RESUMEN

BACKGROUND: Exposure to PM2.5 has been implicated in a range of detrimental health effects, particularly affecting the respiratory system. However, the precise underlying mechanisms remain elusive. METHODS: To address this objective, we collected ambient PM2.5 and administered intranasal challenges to mice, followed by single-cell RNA sequencing (scRNA-seq) to unravel the heterogeneity of neutrophils and unveil their gene expression profiles. Flow cytometry and immunofluorescence staining were subsequently conducted to validate the obtained results. Furthermore, we assessed the phagocytic potential of neutrophils upon PM2.5 exposure using gene analysis of phagocytosis signatures and bacterial uptake assays. Additionally, we utilized a mouse pneumonia model to evaluate the susceptibility of PM2.5-exposed mice to Pseudomonas aeruginosa infection. RESULTS: Our study revealed a significant increase in neutrophil recruitment within the lungs of PM2.5-exposed mice, with subclustering of neutrophils uncovering subsets with distinct gene expression profiles. Notably, exposure to PM2.5 was associated with an expansion of PD-L1high neutrophils, which exhibited impaired phagocytic function dependent upon PD-L1 expression. Furthermore, PM2.5 exposure was found to increase the susceptibility of mice to Pseudomonas aeruginosa, due in part to increased PD-L1 expression on neutrophils. Importantly, monoclonal antibody targeting of PD-L1 significantly reduced bacterial burden, dissemination, and lung inflammation in PM2.5-exposed mice upon Pseudomonas aeruginosa infection. CONCLUSIONS: Our study suggests that PM2.5 exposure promotes expansion of PD-L1high neutrophils with impaired phagocytic function in mouse lungs, contributing to increased vulnerability to bacterial infection, and therefore targeting PD-L1 may be a therapeutic strategy for reducing the harmful effects of PM2.5 exposure on the immune system.

Asunto(s)

Neumonía , Infecciones por Pseudomonas , Animales , Ratones , Neutrófilos/metabolismo , Material Particulado/toxicidad , Infecciones por Pseudomonas/microbiología , Antígeno B7-H1/metabolismo , Pulmón , Neumonía/metabolismo , Pseudomonas aeruginosa

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C-reactive protein (CRP) belongs to the short-chain pentraxin family and functions as a soluble pattern recognition molecule (PRM) aiding in host defense against pathogens. In the present study, a CRP gene, designated HoCRP, was cloned from Hexagrammos otakii for the first time. The full length of the HoCRP cDNA sequence is 821 bp, which contains an open reading frame (ORF) of 675 bp encoding a 224 amino acid protein. The deduced protein is predicted to have a theoretical isoelectric point (pI) of 5.30 and a molecular weight of 25.4 kDa. The recombinant HoCRP protein (rHoCRP) was expressed in E. coli to further characterize the functions of HoCRP. Saccharide binding experiments demonstrated that rHoCRP exhibited a high affinity for various pathogen-associated molecular patterns (PAMPs). Furthermore, bacterial binding and agglutination assays indicated that rHoCRP had the capability to recognize a wide spectrum of microorganisms. These findings suggest that HoCRP functions not only as a PRM for binding PAMPs but also as an immune effector molecule. Considering the role CRP plays in the classical complement pathway, the interaction between rHoCRP and rHoC1q was assessed and proven by a Pull-down and Elisa assay, which implied that rHoCRP may be able to activate complement. In addition, phagocytosis enhancement by rHoCRP in the presence or absence of complement components was analysed by flow cytometry. The results showed that rHoCRP could synergistically enhance the phagocytosis of RAW264.7 cells with complement, providing further evidence of complement activation by rHoCRP through the opsonization of specific complement components. In summary, our findings suggest that rHoCRP may play a crucial role in host antibacterial defense by recognizing pathogens, activating the complement system, and enhancing macrophage function.

Asunto(s)

Proteína C-Reactiva , Perciformes , Animales , Proteína C-Reactiva/genética , Secuencia de Aminoácidos , Escherichia coli/metabolismo , Moléculas de Patrón Molecular Asociado a Patógenos , Proteínas Recombinantes/metabolismo , Fagocitosis , Perciformes/metabolismo

RESUMEN

Aim To study the anti-inflammatory activ¬ity of diterpenes from Tripterygium wilfordii on lipopo- lysaccharide ( LPS)-induced macrophage and its mech¬anism. Methods MTT assay was used to detect the cytotoxicity of compounds. The Griess method was used to detect the NO on LPS-induced RAW264. 7 cells. ELISA was applied to determine the contents of inter- leukin 6 (IL-6) , tumor necrosis factor a ( TNF-a ) , interleukin lp (IL-lfj) and interleukin 18 (IL-18) in cell culture supernatant. Western blot was used to de¬tect IkBcx, .INK, ERK, p38, STAT3 and their phos-phorylation in LPS-induced RAW264.7, as well as the effect on COX-2, iNOS, NLRP3, caspase-1 , cleaved- caspase-1. Flow cytometry was employed to detect the effects of compounds on the phagocytosis of RAW 264. 7 cells. Results Hypoglicin II (1) and ent-pimara-8 (14) , 15-diene-19-ol (6) , two diterpenoid compounds from Tripterygium wilfordii could effectively inhibit the expression of inflammatory mediators ( COX-2 and iN- OS) and inflammatory cytokines (IL-6, IL-lp, IL- 18) in LPS-induced RAW264. 7 cells. Further re¬search found that the phosphorylation of IkBcx , JNK, ERK, P38, STAT3 and NLRP3 was all inhibited; however, there was no significant effect on the expres¬sion of IkBcx, JNK, ERK, P38 and STAT3. At the same time, they also inhibited the phagocytosis of mac-rophages. Conclusions The anti-inflammatory mecha¬nism of Tripterygium wilfordii diterpenoids 1 and 6 might be through inhibiting the production of NLRP3 inflammatory bodies, inflammatory mediators (COX-2 and iNOS) and inflammatory cytokines (IL-6, IL-lp and IL-18) , which is closely related to inhibiting the activation of MAPK, NF-kB and STAT3 pathway.

RESUMEN

BACKGROUND: Intracerebral hemorrhage (ICH) is one of the most lethal stroke types and lacks effective therapeutic regimens. Recently, evidence has suggested the involvement of the ferroptosis inhibitor ferrostatin-1 (Fer-1) in the pathophysiological process of ICH. In this study, we examined the underlying mechanism. METHODS: We induced an in vitro apoptosis model in organotypic hippocampal slice (OHS) using hemoglobin (Hb) and an in vivo ICH model using collagenase. OHSs were treated with MK-801, Fer-1, glutamate, and Hb to assess the impacts of Fer-1 on neuron apoptosis, glutathione peroxidase-4 activity, reactive oxygen species production, inflammation-related factors, expression of M1 markers and M2 markers, and the phagocytic function of microglial cells in vitro. Then, ICH mice were treated with Fer-1 and ruxolitinib to evaluate the effects of Fer-1-orchestrating janus kinase 1/signal transducer and activator of transcription 6 pathway on neurological function, brain water content, hematoma volume, the anti-inflammatory factor, M1 and M2 markers, and the phagocytic function of microglial cells in vivo. RESULTS: Hb or glutamate facilitated glutathione peroxidase dysfunction, reactive oxygen species production, and neuronal apoptosis in OHSs, which was nullified by Fer-1. Fer-1 polarized microglial cells to the M2 phenotype, enhanced their phagocytic function, and prevented inflammation in Hb-induced OHSs. In the ICH mouse model, Fer-1 was found to improve neurological function and promote hematoma absorption. In addition, Fer-1 activated the Fer-1-orchestrating janus kinase 1/signal transducer and activator of transcription 6 pathway, which accelerated microglial M2 polarization, enhanced the phagocytic function of microglial cells, and restrained inflammation in ICH mice. CONCLUSIONS: Overall, our findings suggest that Fer-1 may be a novel mechanism underlying microglial M2 polarization and inflammation after ICH.

Asunto(s)

Hemorragia Cerebral , Ciclohexilaminas , Microglía , Fenilendiaminas , Animales , Ciclohexilaminas/farmacología , Glutamatos/farmacología , Glutatión Peroxidasa/metabolismo , Hematoma , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Janus Quinasa 1/metabolismo , Ratones , Ratones Endogámicos C57BL , Microglía/efectos de los fármacos , Fenotipo , Fenilendiaminas/farmacología , Especies Reactivas de Oxígeno/metabolismo , Factor de Transcripción STAT6/metabolismo

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BACKGROUND AND AIM OF THE WORK: Ketogenic diet (KD) is one of the treatments in drug-resistant epilepsy (DRE). The current study aimed at assessing the effect of KD-induced ketosis on different immunological cells since ketosis is reported to affect neutrophil function. METHODOLOGY: We recruited 21 pediatric patients diagnosed with DRE assigned to start KD. Anthropometric measurements, complete blood picture with differential count, phagocytic function, lymphocyte subsets, and IgG estimation were estimated initially and after 6 months of KD. RESULTS: There were no differences between the initial total leucocytic, neutrophil, and lymphocytic counts as well as the lymphocyte subsets, and the values after 6 months of KD. IgG values showed significant increase yet the values were still within the reference ranges. For the innate immune system, the phagocytic index was assessed and it showed a marked statistical reduction in patients after KD. CONCLUSION: KD has no effect on neutrophil and lymphocytic counts as well as the number of adaptive and immune cells; nevertheless, it causes a reduction in phagocytic index in DRE. Accordingly, further detailed study for the full immunological profile and function is needed to ensure the safety of this therapeutic line and correlate it with the clinical history.

Asunto(s)

Dieta Cetogénica , Epilepsia Refractaria , Preparaciones Farmacéuticas , Niño , Epilepsia Refractaria/diagnóstico , Humanos , Valores de Referencia , Resultado del Tratamiento

RESUMEN

OBJECTIVE: This study aimed to investigate the optimal conditions for producing 68Ga-labeled tin colloid and the feasibility of 68Ga-tin colloid positron emission tomography (PET) for visualization and evaluation of the phagocytic function of Kupffer cells (KCs) in vivo. METHODS: 68Ga-tin colloid was prepared by adding tin solution (1 mM, 0.2 mL) to 68Ga solution (1.0 mL), followed by pH adjustment with sodium acetate (1 M, 0.2 mL). Various labeling times were tested to find the optimal one. Colloid size was measured by filtering the solution through three-ply membrane filters (with pore sizes of 200, 3000, and 5000 nm), and radioactivity was measured in the whole filtrate and the filters using a gamma counter. The in vitro stability of the colloid was evaluated by the size measurement after incubation under ambient conditions for up to 60 min. PET scanning was performed for 30 min after intravenous administration of 68Ga-tin colloid solution (4 MBq) to healthy rats. Time-activity-curves for the liver, spleen, and blood pool were generated. Finally, liver uptake was compared before and after the establishment of KC-depletion and non-alcoholic steatohepatitis (NASH) rat models. RESULTS: Colloid size increased with increasing labeling time. After pH adjustment, the colloid sizes remained nearly unchanged. The optimal labeling time was determined as 30 min. PET imaging of healthy rats revealed that liver uptake of the 68Ga-tin colloid increased with increasing colloid size. In KC-depleted rats, liver uptake significantly decreased (n = 4, p < 0.01). NASH model rats showed significantly decreased uptake of 68Ga-tin colloid in the livers (n = 5, p < 0.01). CONCLUSIONS: 68Ga-tin colloid, prepared by a simple radiolabeling method, enabled in vivo PET imaging to evaluate the phagocytic function of KCs.

Asunto(s)

Radioisótopos de Galio/química , Macrófagos del Hígado/inmunología , Fagocitosis , Tomografía de Emisión de Positrones/métodos , Estaño/química , Animales , Coloides , Marcaje Isotópico , Ratas , Estaño/farmacocinética

RESUMEN

BACKGROUND: We previously reported that maternal alcohol use significantly increases the risk of sepsis in premature and term newborns. In the mouse, fetal ethanol exposure results in an immunosuppressed phenotype for the alveolar macrophage (AM) and decreases bacterial phagocytosis. In pregnant mice, ethanol decreased AM zinc homeostasis, which contributed to immunosuppression and impaired AM phagocytosis. In this study, we explored whether ethanol-induced zinc insufficiency extended to the pup AMs and contributed to immunosuppression and exacerbated viral lung infections. METHODS: C57BL/6 female mice were fed a liquid diet with 25% ethanol-derived calories or pair-fed a control diet with 25% of calories as maltose-dextrin. Some pup AMs were treated in vitro with zinc acetate before measuring zinc pools or transporter expression and bacteria phagocytosis. Some dams were fed additional zinc supplements in the ethanol or control diets, and then we assessed pup AM zinc pools, zinc transporters, and the immunosuppressant TGFß1. On postnatal day 10, some pups were given intranasal saline or respiratory syncytial virus (RSV), and then AM RSV phagocytosis and the RSV burden in the airway lining fluid were assessed. RESULTS: Fetal ethanol exposure decreased pup AM zinc pools, zinc transporter expression, and bacterial clearance, but in vitro zinc treatments reversed these alterations. In addition, the expected ethanol-induced increase in TGFß1 and immunosuppression were associated with decreased RSV phagocytosis and exacerbated RSV infections. However, additional maternal zinc supplements blocked the ethanol-induced perturbations in the pup AM zinc homeostasis and TGFß1 immunosuppression, thereby improving RSV phagocytosis and attenuating the RSV burden in the lung. CONCLUSION: These studies suggest that, despite normal maternal dietary zinc intake, in utero alcohol exposure results in zinc insufficiency, which contributes to compromised neonatal AM immune functions, thereby increasing the risk of bacterial and viral infections.

Asunto(s)

Trastornos del Espectro Alcohólico Fetal/etiología , Macrófagos Alveolares/efectos de los fármacos , Infecciones por Virus Sincitial Respiratorio/etiología , Zinc/deficiencia , Animales , Suplementos Dietéticos , Modelos Animales de Enfermedad , Femenino , Trastornos del Espectro Alcohólico Fetal/inmunología , Trastornos del Espectro Alcohólico Fetal/fisiopatología , Tolerancia Inmunológica , Macrófagos Alveolares/fisiología , Ratones , Ratones Endogámicos C57BL , Embarazo , Infecciones por Virus Sincitial Respiratorio/inmunología , Infecciones por Virus Sincitial Respiratorio/fisiopatología

RESUMEN

INTRODUCTION: There is a possible association between obesity and infections. We sought to investigate phagocytic functions in obese children and their relation to serum leptin levels. METHODS: A cross sectional, controlled study was conducted, comprising 40 cases with simple visceral-type obesity. Subjects were evaluated for percentage of caloric intake, frequency and type of infections, body mass index (BMI) z score, in addition to complete blood counting, serum leptin assay (ELISA) and Dihydrorhodamine (DHR) flowcytometry. RESULTS: Cases were 21 males (52.5%) and 19 females (47.5%) with mean age 7.14 years±2.73 SD with median duration of obesity 4.2 years (IQR: 2-6). Cases had higher frequency of infections compared with controls (p<0.001). Serum leptin was significantly higher among cases (t=-12.391, p<0.001), while DHR results were comparable in the studied groups (p=0.067). Among cases, absolute lymphocytic count (ALC) correlated negatively with percentage of total caloric intake (p=0.045). Leptin levels correlated positively with frequency of infections (p=0.019) but negatively with ALC (p=0.043). DHR results showed weak negative correlations with serum leptin (p=0.177) and with BMI Z score (p=0.109). CONCLUSION: Obese children are posed at increased risk of infections and have higher serum leptin levels with possible negative effects of leptin on phagocytic functions.

Asunto(s)

Enfermedades Transmisibles/epidemiología , Leptina/sangre , Obesidad Infantil/epidemiología , Fagocitosis , Recuento de Células Sanguíneas , Índice de Masa Corporal , Niño , Preescolar , Enfermedades Transmisibles/etiología , Enfermedades Transmisibles/microbiología , Estudios Transversales , Ingestión de Energía , Femenino , Humanos , Masculino , Obesidad Infantil/sangre , Obesidad Infantil/microbiología

RESUMEN

OBJECTIVE： To investigate the effects of benzoxazole derivative 2-（chlorobenzoxazolyl-2-yl）-4，5，6，7-tetrahydro- dihydro-indazole-3-ol （PO-296） on the differentiation of murine bone marrow-derived dendritic cells（DC） and their related indexes as specific surface molecules and inflammatory cytokines. METHODS： Bone marrow nuclear cells of mice were isolated， and immature DC （imDC） was obtained by recombinant mice granulocyte macrophage colony-stimulating factor and recombinant mice IL-4. After pretreated with low-dose， medium-dose and high-dose （1， 5， 25 μmol/L） of PO-296， DC was obtained by lipopolysaccharide induction. Flow cytometry was used to detect the expression of DC specific surface molecules [i.e. the proportion of class Ⅱ major histocompatibility complex （MHC Ⅱ）， CD80， CD86 and chemokine receptor 7 （CCR7） positive cells]， imDC phagocytosis （i.e. the proportion of dextran positive cells） and DC survival （i.e. the proportion of survival cells）. ELISA method was used to detect the levels of inflammatory cytokines （IL-10， IL-12 and TNF-α） in cell culture medium. RESULTS： Compared with imDC group， the proportion of MHC Ⅱ， CD80 and CD86 positive cells were increased significantly in non-loading group （P＜0.05）. Compared with non-loading group， the levels of IL-10 in cell culture medium were increased significantly in PO-296 groups. The proportions of MHC Ⅱ， CD80 and CD86 positive cells in positive group and PO-296 medium-dose and high-dose groups as well as the levels of IL-12 and TNF-α in cell culture medium in administration groups were decreased significantly （P＜0.05）. There was no statistical significance in the proportion of CCR7 positive cells， dextran positive cells and survival cells in administration groups， compared with non-loading group （P＞0.05）. CONCLUSIONS： PO-296 has no obvious cytotoxicity and does not affect the phagocytic function of imDC. At the same time， the compound can inhibit the expression of DC specific surface molecules and regulate the secretion of inflammatory cytokines.

RESUMEN

Lung macrophages (LMs) are essential immune effector cells that are pivotal in both innate and adaptive immune responses to inhaled foreign matter. They either reside within the airways and lung tissues (from early life) or are derived from blood monocytes. Similar to macrophages in other organs and tissues, LMs have natural plasticity and can change phenotype and function depending largely on the microenvironment they reside in. Phenotype changes in lung tissue macrophages have been implicated in chronic inflammatory responses and disease progression of various chronic lung diseases, including Chronic Obstructive Pulmonary Disease (COPD). LMs have a wide variety of functional properties that include phagocytosis (inorganic particulate matter and organic particles, such as viruses/bacteria/fungi), the processing of phagocytosed material, and the production of signaling mediators. Functioning as janitors of the airways, they also play a key role in removing dead and dying cells, as well as cell debris (efferocytic functions). We herein review changes in LM phenotypes during chronic lung disease, focusing on COPD, as well as changes in their functional properties as a result of such shifts. Targeting molecular pathways involved in LM phenotypic shifts could potentially allow for future targeted therapeutic interventions in several diseases, such as COPD.

Asunto(s)

Inflamación/inmunología , Pulmón/inmunología , Macrófagos Alveolares/inmunología , Enfermedad Pulmonar Obstructiva Crónica/inmunología , Inmunidad Adaptativa/inmunología , Humanos , Inmunidad Innata/inmunología , Inflamación/patología , Pulmón/patología , Macrófagos Alveolares/patología , Monocitos/inmunología , Fagocitosis/inmunología , Enfermedad Pulmonar Obstructiva Crónica/patología , Fumar/efectos adversos

RESUMEN

OBJECTIVE: Atopic dermatitis (AD) is a skin disorder clinically seen in the pediatric population. It is well recognized that patients with AD have an increased susceptibility to cutaneous colonization and infection with bacteria, fungi, and viruses. This study was undertaken to investigate the phagocytic activity and chemotactic response of mononuclear and polymorphonuclear leukocytes in severe AD patients. METHODS: A total of 50 children with severe AD were selected according to severity scoring of AD (the SCORAD index) and 30 healthy children of same age and sex were also selected as controls. The mononuclear and neutrophilic leukocytes were separated and the phagocytic ingestion of zymosan particles was determined. Migration distance in response tobacterial lipopolysaccharide chemotactic factor was also determined. Immunological disturbance in AD patients was determined by sandwich enzyme-liked immunosorbent assays for total serum immunoglobulin E (IgE), complement 3 (C3) C4. RESULTS: Of 50 AD patients with severe disease activity, 36 patients (72%) showed reduction in mononuclear and neutrophilic phagocytic activity. Children with AD had higher levels of total serum IgE, C3, and C4 compared to healthy children (P < 0.01). CONCLUSIONS: The study results demonstrated an inhibition in the chemotactic response and phagocytic activity by mononuclear and/or neutrophilic leukocytes in severe AD patients. We further observed an involvement of perturb complement system in patients with AD. Hence, we clearly showed that AD is exacerbated with compromised immunological response, especially the innate immune response.

RESUMEN

Neutrophil granulocytes and monocytes have been intensively studied, but there is no scientific data on one of their most important functions, namely the phagocyte function in pregnancy and preeclampsia. The aim of this study was to examine this function. Twenty-five healthy pregnant, 25 preeclamptic pregnant, and 20 healthy, non-pregnant women were enrolled into our study. Cells were isolated from peripheral blood samples, marked and evaluated for the phagocytic index with an immunofluorescent microscope after phagocytosing the zymosan molecules. The phagocytic function of monocytes and neutrophil granulocytes decreased significantly in healthy pregnancy compared with non-pregnant women and in preeclampsia, and it decreased significantly compared with healthy pregnancy. Decreased phagocytic function in healthy pregnancy can be a part of the maternal immunosuppression, which is essential for the protection of the hemiallograft fetus. Further reduction of phagocytic function may be one of the immunoregulatory abnormalities found in preeclampsia.

Asunto(s)

Monocitos/inmunología , Neutrófilos/inmunología , Fagocitosis , Preeclampsia/inmunología , Adulto , Femenino , Humanos , Monocitos/metabolismo , Monocitos/patología , Neutrófilos/metabolismo , Neutrófilos/patología , Preeclampsia/sangre , Preeclampsia/patología , Embarazo

RESUMEN

PURPOSE: To evaluate the Kupffer cell (KC) phagocytic function using superparamagnetic iron oxide-enhanced magnetic resonance imaging (SPIO-MRI) in animal models with nonalcoholic fatty liver disease (NAFLD). MATERIALS AND METHODS: Mouse NAFLD models with varying severity were created by feeding high-fat, high-cholesterol (HFHC) diets to ob/ob mice for 3, 6, or 12 weeks. SPIO-MRI was performed on a 4.7-T animal scanner in the mouse NAFLD models, in wildtype control mouse, and in the NAFLD mice (NAFLD treatment group) that received 6 weeks of pioglitazone treatment. The relative signal loss (RSL) of the liver was measured in each animal to represent the magnitude of SPIO-induced signal loss of the liver. Liver samples were analyzed for steatosis, inflammation, fibrosis, and the number of SPIO particles and KCs. RESULTS: RSL values of the NAFLD mice (range of RSL value, 26.3%-53.8%) seen on SPIO-MRI were significantly lower than those of the control mice (67.7%-74.8%, P ≤ 0.008) and decreased in proportion to the duration of their HFHC diet (mean ± SD, 53.7% ± 10.9, 44.7% ± 8.2, and 26.3% ± 12.6, after 3-, 6-, and 12-week HFHC diet, respectively, on 20-minute delayed images). For the NAFLD treatment group, the RSL values increased after 6 weeks of pioglitazone treatment, compared with the values before treatment (P ≤ 0.039). The RSL values had significant independent correlation with both hepatic steatosis (P = 0.007) and inflammation (P = 0.023). CONCLUSION: KC phagocytic dysfunction is aggravated in the progression of NAFLD and may be reversible with therapeutic intervention. SPIO-MRI may be useful for classifying the severity of NAFLD and monitoring the treatment response of NAFLD.

Asunto(s)

Dextranos , Macrófagos del Hígado/patología , Imagen por Resonancia Magnética/métodos , Nanopartículas de Magnetita , Enfermedad del Hígado Graso no Alcohólico/patología , Enfermedad del Hígado Graso no Alcohólico/fisiopatología , Fagocitosis , Animales , Medios de Contraste , Aumento de la Imagen/métodos , Interpretación de Imagen Asistida por Computador/métodos , Masculino , Ratones , Ratones Endogámicos C57BL , Reproducibilidad de los Resultados , Sensibilidad y Especificidad

RESUMEN

It has been reported that host defense responses, such as phagocytic function of neutrophils and natural killer (NK) cell activity of lymphocytes, are impaired in cirrhotic patients. This review will concentrate on the impairment of innate immune responses in decompensated cirrhotic patients and the effect of the treatment by branched-chain amino acids (BCAA) on innate immune responses. We already reported that phagocytic function of neutrophils was significantly improved by 3-mo BCAA supplementation. In addition, the changes of NK activity were also significant at 3 mo of supplementation compared with before supplementation. Also, Fisher's ratios were reported to be significantly increased at 3 mo of BCAA supplementation compared with those before oral supplementation. Therefore, administration of BCAA could reduce the risk of bacterial and viral infection in patients with decompensated cirrhosis by restoring impaired innate immune responses of the host. In addition, it was also revealed that BCAA oral supplementation could reduce the risk of development of hepatocellular carcinoma in cirrhotic patients. The mechanisms of the effects will also be discussed in this review article.

Asunto(s)

Aminoácidos de Cadena Ramificada/uso terapéutico , Suplementos Dietéticos , Inmunidad Innata/efectos de los fármacos , Cirrosis Hepática/tratamiento farmacológico , Administración Oral , Aminoácidos de Cadena Ramificada/administración & dosificación , Carcinoma Hepatocelular/inmunología , Carcinoma Hepatocelular/prevención & control , Humanos , Células Asesinas Naturales/efectos de los fármacos , Células Asesinas Naturales/inmunología , Cirrosis Hepática/complicaciones , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/inmunología , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/prevención & control , Neutrófilos/efectos de los fármacos , Neutrófilos/inmunología , Fagocitosis/efectos de los fármacos , Factores de Riesgo , Resultado del Tratamiento

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Surgery alters the body's homeostatic balance and defense mechanisms. In adults transient postoperative cellular and humoral immunosuppression after different degrees of operative stress has been reported. In children the immunologic consequences of operations are not elaborated. This study investigates the effect of minor and major surgery on early nonspecific immune response in terms of neutrophil counts and function. Forty-three children undergoing minor and major elective procedures were studied. Blood samples were collected before, immediately after, and 72 h after surgery. Total white cell count, differential neutrophil count, and neutrophil phagocytic function were studied using nitroblue tetrazolium test. Children were divided into two groups-group 1 underwent minor surgery and group 2 major surgery. In group 1 there was a significant drop in total counts after surgery, but in group 2 total counts were not affected. In both groups, the percentage of neutrophils increased immediately after surgery but fell to near or less than preoperative levels 72 h after surgery. However, the assessment of neutrophil functions by nitroblue tetrazolium test in both unstimulated and stimulated forms revealed it to be unchanged in group 1. In group 2 the unstimulated neutrophil function was elevated 72 h after surgery, whereas stimulated function was elevated immediately after surgery. Minor surgery does not alter the early nonspecific immune response. However, major surgery seems to induce a transient increase in neutrophil phagocytic activity.

RESUMEN

Chronic alcohol abuse increases lung oxidative stress and susceptibility to respiratory infections by impairing alveolar macrophage (AM) function. NADPH oxidases (Nox) are major sources of reactive oxygen species in AMs. We hypothesized that treatment with the critical antioxidant glutathione (GSH) attenuates chronic alcohol-induced oxidative stress by downregulating Noxes and restores AM phagocytic function. Bronchoalveolar lavage (BAL) fluid and AMs were isolated from male C57BL/6J mice (8-10 wk) treated ± ethanol in drinking water (20% wt/vol, 12 wk) ± orally gavaged GSH in methylcellulose vehicle (300 mg x kg(-1) x day(-1), during week 12). MH-S cells, a mouse AM cell line, were treated ± ethanol (0.08%, 3 days) ± GSH (500 µM, 3 days or last 1 day of ethanol). BAL and AMs were also isolated from ethanol-fed and control mice ± inoculated airway Klebsiella pneumoniae (200 colony-forming units, 28 h) ± orally gavaged GSH (300 mg/kg, 24 h). GSH levels (HPLC), Nox mRNA (quantitative RT-PCR) and protein levels (Western blot and immunostaining), oxidative stress (2',7'-dichlorofluorescein-diacetate and Amplex Red), and phagocytosis (Staphylococcus aureus internalization) were measured. Chronic alcohol decreased GSH levels, increased Nox expression and activity, enhanced oxidative stress, impaired phagocytic function in AMs in vivo and in vitro, and exacerbated K. pneumonia-induced oxidative stress. Although how oral GSH restored GSH pools in ethanol-fed mice is unknown, oral GSH treatments abrogated the detrimental effects of chronic alcohol exposure and improved AM function. These studies provide GSH as a novel therapeutic approach for attenuating alcohol-induced derangements in AM Nox expression, oxidative stress, dysfunction, and risk for pneumonia.

Asunto(s)

Alcoholismo/inmunología , Antioxidantes/metabolismo , Glutatión/metabolismo , Macrófagos Alveolares/inmunología , NADH NADPH Oxidorreductasas/metabolismo , Alcoholismo/metabolismo , Animales , Antioxidantes/farmacología , Líquido del Lavado Bronquioalveolar/inmunología , Línea Celular , Depresores del Sistema Nervioso Central/farmacología , Regulación hacia Abajo/efectos de los fármacos , Regulación hacia Abajo/inmunología , Activación Enzimática/efectos de los fármacos , Activación Enzimática/inmunología , Etanol/farmacología , Glutatión/farmacología , Infecciones por Klebsiella/inmunología , Infecciones por Klebsiella/metabolismo , Klebsiella pneumoniae/inmunología , Macrófagos Alveolares/efectos de los fármacos , Macrófagos Alveolares/metabolismo , Masculino , Glicoproteínas de Membrana/metabolismo , Ratones , Ratones Endogámicos C57BL , NADPH Oxidasa 1 , NADPH Oxidasa 2 , NADPH Oxidasa 4 , NADPH Oxidasas/metabolismo , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/inmunología , Fosfoproteínas/metabolismo

RESUMEN

Objective: To investigate the effect of total flavones from the leaves of Choerospondias axillaris (TFLCA) on the immune function of normal mice and to provide the experimental basis for the reasonable application of C. axillaris. Methods: The carbon clearance method, cutaneous delayed hypersensitivity reaction method, serum hemolysin method, and index of immune organs were used to study the effect of TFLCA on the immune function of mice. Results: TFLCA could enhance the phagocytic function of mononuclear macrophage and the cutaneous delayed hypersensitivity reaction of mice, and increase the content of hemolysin antibody and the thymus index in mice. Conclusion: TFLCA could improve the celiac macrophage activity and specific immunity of mice, and TFLCA, consisting with the total flavones of Choerospondiatis Fructus (TFCF), has the effect on the immune function of mice. So both TFLCA and TFCF have the regulatory effects on the immune function of mice. © 2013 Tianjin Press of Chinese Herbal Medicines.

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INTRODUCTION: Whey protein contains biologically active ingredients that can prevent and attenuate disease besides being nutritive. The aim of the study was to clarify the effects of oral administration of whey protein on viral load and host defence mechanisms, in particular, phagocytic function of neutrophils, selected immunomodulatory cytokines and serum inflammatory markers, in compensated chronic hepatitis C virus (HCV) patients. MATERIAL AND METHODS: Twenty-seven HCV patients (20 males and 7 females) recruited from the hepatology clinic of the Theodor Bilharz Research Institute (TBRI) were given whey protein concentrate (WPC) twice daily for two months. In addition, 15 age and sex matched healthy participants were included in the study, as a control group. Neutrophil phagocytic activity, serum intercellular adhesion molecule (sICAM), interleukin-2 (IL-2), nitric oxide (NO), as well as HCV-RNA levels and routine investigations were determined for patients, before and after WPC supplementation and once for the control group. RESULTS: There was a significant decrease in viral load and markers of active inflammation, alanine aminotransferase (ALT) and aspartate aminotransferase (AST), while serum albumin, total leucocyte counts and absolute neutrophil counts showed significant elevation accompanied by improvement of neutrophil phagocytic activity after WPC supplementation compared to pre-treated levels. The oral WPC supplementation was well tolerated without any serious adverse events. CONCLUSIONS: Oral supplementation of WPC has promising results as a new therapeutic strategy against HCV and its sequelae by decreasing the viral load and active inflammation as well as improving the synthetic capacity of the liver and the phagocytic function of neutrophils, in these patients.

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El Ateromixol es un producto desarrollado por el Centro Nacional de Investigaciones Científicas y comercializado por los Laboratorios Delmer de Ciudad de La Habana. Tiene como principio activo al policosanol, constituido por una mezcla de alcoholes primarios alifáticos superiores obtenido de la cera de Saccharum officinarum L. Se estudió el efecto in vitro del Ateromixol, conocido como PPG, sobre los linfocitos y neutrófilos de 15 donantes voluntarios de sangre y de 15 enfermos con diagnóstico de inmunodeficiencia celular mediante la prueba de transformación linfoblástica, con el empleo de timidina tritiada, la técnica de roseta activa y la prueba de función fagocítica. No se observaron diferencias significativas en el análisis estadístico de las condiciones experimentales sin Ateromixol y con diluciones desde 500 m g/mL hasta 3,90 m g/mL.

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Ateromixol is a product developed by the National Center of Scientific Research and commercialized by Delmer Laboratories of Havana City . Its active principle is polycosanol, which is composed of a mixture of primary aliphatic higher alcohols obtained from the wax of Saccharum officinarum L. The effect in vitro of Ateromixol, known as PPG, on the lymphocytes and neutrophiles of 15 voluntary blood donors with diagnosis of cellular immunodeficiency was studied by the lymphoblastic transformation test, with the use of tritiated timidine, the active rosette technique and the phagocytic function test. No significant differences were observed in the statistical analysis of the experimental conditions without Ateromixol and with dilutions from 500 m g/mL to 3.90 m g/mL.

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Objective To evaluate the influences of high hydrostatic pressure (HHP) on the virulence and antigenicity of Coxsackie virus B3 (CB3 V) , to explore a new physiological method to develop an active vaccine against Coxsackie virus. Methods The phagocytosis of the macrophages in mice to the CB3 V and the TCID50 of the CB3V before and after treated by HHP were examined. Results TCID50 increased from 10-5 to 10-4 when treated by 680 MPa; viruses were inactivated at 700 MPa. Viruses were also inactivated by the pressure less than 700 MPa, but needed prolonged time. The phagocytic function, antibody and T lymphocyte transformation rate in experimental mice (heated, attenuated, and inactive viruses) exhibited a significant difference compared with control mice (P