RESUMEN

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains as a leading infectious cause of death worldwide. The increasing number of multidrug-resistant TB (MDR-TB) cases contributes to the poor control of the TB epidemic. Currently, little is known about the immunological requirements of protective responses against MDR-TB. This is of major relevance to identify immune markers for treatment monitoring and targets for adjuvant immunotherapies. Here, we hypothesized that MDR-TB patients display unique immunophenotypical features and immune cell migration dynamics compared to drug-sensitive TB (DS-TB). Hence, we prospectively conducted an extensive characterization of the immune profile of MDR-TB patients at different time points before and after pharmacological therapy. For this purpose, we focused on the leukocyte expression of chemokine receptors, distribution of different monocyte and lymphocyte subsets, plasma levels of chemotactic factors, and in vitro migration capacity of immune cells. Our comparative cohort consisted of DS-TB patients and healthy volunteer donors (HD). Our results demonstrate some unique features of leukocyte migration dynamics during MDR-TB. These include increased and prolonged circulation of CD3+ monocytes, CCR4+ monocytes, EM CD4+ T cells, EM/CM CD8+ T cells, and CXCR1+CXCR3+ T cells that is sustained even after the administration of anti-TB drugs. We also observed shared characteristics of both MDR-TB and DS-TB that include CCR2+ monocyte depletion in the blood; high plasma levels of MPC-1, CCL-7, and IP-10; and increased responsiveness of leukocytes to chemotactic signals in vitro. Our study contributes to a better understanding of the MDR-TB pathobiology and uncovers immunological readouts of treatment efficacy.

Asunto(s)

Antituberculosos/farmacología , Leucocitos Mononucleares/inmunología , Receptores de Quimiocina/metabolismo , Tuberculosis Resistente a Múltiples Medicamentos/inmunología , Tuberculosis Pulmonar/inmunología , Adulto , Antituberculosos/uso terapéutico , Biomarcadores/análisis , Biomarcadores/metabolismo , Estudios de Casos y Controles , Movimiento Celular/inmunología , Monitoreo de Drogas/métodos , Estudios de Seguimiento , Voluntarios Sanos , Humanos , Leucocitos Mononucleares/metabolismo , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/inmunología , Mycobacterium tuberculosis/aislamiento & purificación , Estudios Prospectivos , Receptores de Quimiocina/análisis , Tuberculosis Resistente a Múltiples Medicamentos/sangre , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Pulmonar/sangre , Tuberculosis Pulmonar/tratamiento farmacológico , Tuberculosis Pulmonar/microbiología

RESUMEN

The present study aims to evaluate the longitudinal effects of induced experimental infections in gnotoxenic animals on the expression of inflammatory chemokines and their receptors in periradicular tissues. The null hypothesis tested was that Enterococcus faecalis and Fusobacterium nucleatum had no effect on CCR5, CCL5, CXCL10, CCL2/MCP-1, CXCR2 and CCR1 expression. Two groups of five animals (n = 5) aged between 8 and 12 weeks were used in this study. The animals were anaesthetized, and coronary access was performed in the first molar on the right and left sides. Microorganisms were inoculated into the left molar, and the right molar was sealed without contamination to function as a control. Animals were sacrificed 7 and 14 days after infection, and periapical tissues were collected. The cytokine mRNA expression levels were assessed using real-time PCR. The chemokine mRNA expression levels demonstrated that the experimental infection was capable of inducing increased chemokine expression on day 7 compared to that on day 14, except for CCR5 and CCL5, which showed no changes. The gnotoxenic animal model proved to be effective and allowed evaluation of the immune response against a known infection. Additionally, this study demonstrates that gene expression of chemokines and their receptors against the experimental infection preferentially prevailed during the initial phase of induction of the periradicular alteration (i.e., on day 7 post-infection).

Asunto(s)

Quimiocinas/análisis , Cavidad Pulpar/inmunología , Enfermedades de la Pulpa Dental/inmunología , Infecciones por Fusobacterium/inmunología , Vida Libre de Gérmenes , Infecciones por Bacterias Grampositivas/inmunología , Receptores de Quimiocina/análisis , Animales , Quimiocinas/genética , Cavidad Pulpar/microbiología , Enfermedades de la Pulpa Dental/microbiología , Expresión Génica , Ratones , Enfermedades Periapicales/inmunología , Enfermedades Periapicales/microbiología , Reacción en Cadena en Tiempo Real de la Polimerasa , Receptores de Quimiocina/genética , Valores de Referencia , Factores de Tiempo

RESUMEN

Abstract The present study aims to evaluate the longitudinal effects of induced experimental infections in gnotoxenic animals on the expression of inflammatory chemokines and their receptors in periradicular tissues. The null hypothesis tested was that Enterococcus faecalis and Fusobacterium nucleatum had no effect on CCR5, CCL5, CXCL10, CCL2/MCP-1, CXCR2 and CCR1 expression. Two groups of five animals (n = 5) aged between 8 and 12 weeks were used in this study. The animals were anaesthetized, and coronary access was performed in the first molar on the right and left sides. Microorganisms were inoculated into the left molar, and the right molar was sealed without contamination to function as a control. Animals were sacrificed 7 and 14 days after infection, and periapical tissues were collected. The cytokine mRNA expression levels were assessed using real-time PCR. The chemokine mRNA expression levels demonstrated that the experimental infection was capable of inducing increased chemokine expression on day 7 compared to that on day 14, except for CCR5 and CCL5, which showed no changes. The gnotoxenic animal model proved to be effective and allowed evaluation of the immune response against a known infection. Additionally, this study demonstrates that gene expression of chemokines and their receptors against the experimental infection preferentially prevailed during the initial phase of induction of the periradicular alteration (i.e., on day 7 post-infection).

Asunto(s)

Animales , Ratones , Infecciones por Bacterias Grampositivas/inmunología , Quimiocinas/análisis , Receptores de Quimiocina/análisis , Cavidad Pulpar/inmunología , Enfermedades de la Pulpa Dental/inmunología , Infecciones por Fusobacterium/inmunología , Vida Libre de Gérmenes , Enfermedades Periapicales/inmunología , Enfermedades Periapicales/microbiología , Valores de Referencia , Factores de Tiempo , Expresión Génica , Quimiocinas/genética , Receptores de Quimiocina/genética , Cavidad Pulpar/microbiología , Enfermedades de la Pulpa Dental/microbiología , Reacción en Cadena en Tiempo Real de la Polimerasa

RESUMEN

Taiep rat has a failure in myelination and remyelination processes leading to a state of hypomyelination throughout its life. Chemokines, which are known to play a role in inflammation, are also involved in the remyelination process. We aimed to demonstrate that remyelination-stimulating factors are altered in the brainstem of 1- and 6-month-old taiep rats. We used a Rat RT(2) Profiler PCR Array to assess mRNA expression of 84 genes coding for cytokines, chemokines, and their receptors. We also evaluated protein levels of CCL2, CCR1, CCR2, CCL5, CCR5, CCR8, CXCL1, CXCR2, CXCR4, FGF2, and VEGFA by ELISA. Sprague-Dawley rats were used as a control. PCR Array procedure showed that proinflammatory cytokines were not upregulated in the taiep rat. In contrast, some mRNA levels of beta and alpha chemokines were upregulated in 1-month-old rats, but CXCR4 was downregulated at their 6 months of age. ELISA results showed that CXCL1, CCL2, CCR2, CCR5, CCR8, and CXCR4 protein levels were decreased in brainstem at the age of 6 months. These results suggest the presence of a chronic neuroinflammation process with deficiency of remyelination-stimulating factors (CXCL1, CXCR2, and CXCR4), which might account for the demyelination in the taiep rat.

Asunto(s)

Quimiocinas/análisis , Vaina de Mielina/metabolismo , Receptores de Quimiocina/análisis , Animales , Quimiocinas/genética , Quimiocinas/metabolismo , Regulación hacia Abajo , Ensayo de Inmunoadsorción Enzimática , Microscopía Fluorescente , Vaina de Mielina/genética , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Ratas Transgénicas , Receptores de Quimiocina/genética , Receptores de Quimiocina/metabolismo , Transcriptoma , Regulación hacia Arriba

RESUMEN

The purpose of the present study was to examine the acute effects of resistance training (RT) on CD4⁺ and CD8⁺ T lymphocytes apoptosis (annexin V⁺) and migration (CX3CR1). Twelve subjects performed two RT sessions (3 sets of 9 exercises) with 1 min (Hyper-1) and 3 min (Hyper-3) of rest-interval length between sets and exercises. CD4⁺ and CD8⁺ cells count displayed no change following Hyper-1 and Hyper-3. There was an increase in the percentage of CD4⁺ positive for annexin V⁺ and CX3CR1⁺ immediately after and 24 h post Hyper-1. Percentage of CD4⁺ positive for annexin V⁺ increased 2 and 24 h post Hyper-3, and decreased after CXCR1⁺ for the same time-points. There was an increase in CD8⁺ positive for annexin V⁺ and CX3CR1⁺ immediately after, 2 and 24 h post Hyper-1 and Hyper-3, while no differences were found between Hyper-1 and Hyper-3. Acute RT increase the apoptosis and migration of CD4⁺ and CD8⁺ lymphocytes even 24h after exercise, with minimal effects of rest-interval length.

Asunto(s)

Apoptosis , Linfocitos T CD4-Positivos/fisiología , Linfocitos T CD8-positivos/fisiología , Movimiento Celular , Entrenamiento de Fuerza , Anexina A5/análisis , Anexina A5/inmunología , Antígenos de Superficie , Biomarcadores/análisis , Relación CD4-CD8 , Linfocitos T CD4-Positivos/citología , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/citología , Linfocitos T CD8-positivos/inmunología , Receptor 1 de Quimiocinas CX3C , Femenino , Humanos , Activación de Linfocitos , Recuento de Linfocitos , Masculino , Receptores de Quimiocina/análisis , Adulto Joven

RESUMEN

This study examines the role of Th1 (interferon-gamma [IFN-gamma]) and Th2 (interleukin-4 [IL-4] and IL-10) cytokines, an intercellular adhesion molecule (ICAM-1), and a chemokine receptor (CCR5) in the pathogenesis of periapical lesions at different stages of development in knockout mice. For lesion induction, the first molar was opened and inoculated with 4 bacterial strains and left open to the oral environment. After 21 and 42 days, the IFN-gamma, IL-10, ICAM-1, and CCR5 knockout animals presented periapical lesions larger than those of wild-type animals. There was no statistically significant difference between periapical lesions induced in IL-4 knockout and wild-type animals during the periods evaluated. Our findings suggest an important role for IFN-gamma, IL-10, ICAM-1, and CCR5 in the pathogenesis of experimentally induced pulp infection and bone destruction as endogenous suppressor of periapical lesion development, whereas IL-4 appears to present a nonsignificant effect on periapical lesion modulation.

Asunto(s)

Molécula 1 de Adhesión Intercelular/fisiología , Interferón gamma/fisiología , Interleucina-10/fisiología , Enfermedades Periapicales/metabolismo , Receptores CCR5/fisiología , Animales , Cavidad Pulpar/metabolismo , Cavidad Pulpar/microbiología , Interleucina-4/fisiología , Masculino , Ratones , Ratones Noqueados , Osteoclastos/citología , Enfermedades Periapicales/microbiología , Receptores de Quimiocina/análisis , Receptores de Quimiocina/deficiencia , Receptores de Quimiocina/metabolismo

RESUMEN

Inflammatory immune reactions in response to periodontopathogens are thought to protect the host against infection, but may trigger periodontal destruction. Thus, we examined the mechanisms by which the proinflammatory cytokine tumour necrosis factor (TNF)-alpha modulates the outcome of Actinobacillus actinomycetemcomitans-induced periodontal disease in mice. Our results showed that TNF-alpha receptor p55-deficient mice [p55TNF-knock-out (KO)] developed a less severe periodontitis in response to A. actinomycetemcomitans infection, characterized by significantly less alveolar bone loss and inflammatory reaction. Real-time polymerase chain reaction (PCR) demonstrated that levels of chemokines (CXCL1, 3 and 10; CCL3 and 5) and their receptors (CXCR2 and 3, CCR5) were lower in p55TNF-KO mice, as were matrix metalloproteinase (MMP)-1, 2 and 9 and receptor activator of nuclear factor kB ligand (RANKL) mRNA levels. However, the absence of the TNF-alpha p55 results in an impairment of protective immunity to A. actinomycetemcomitans infection, characterized by increased bacterial load and higher levels of C-reactive protein during the course of disease. Such impaired host response may be the result of the reduced chemoattraction of lymphocytes, neutrophils and macrophages, and reduced inducible nitric oxide synthase expression (iNOS) and myeloperoxidase (MPO) production in periodontal tissues of p55 TNF-KO mice. Our results demonstrate the mechanisms involved determining periodontal disease severity by TNF-alpha receptor p55, and its role in providing immune protection to A. actinomycetemcomitans periodontal infection.

Asunto(s)

Infecciones por Actinobacillus/inmunología , Aggregatibacter actinomycetemcomitans , Periodontitis/inmunología , Periodoncio/inmunología , Receptores Tipo I de Factores de Necrosis Tumoral/metabolismo , Receptores Señuelo del Factor de Necrosis Tumoral/metabolismo , Infecciones por Actinobacillus/patología , Aggregatibacter actinomycetemcomitans/inmunología , Pérdida de Hueso Alveolar , Animales , Anticuerpos Antibacterianos/sangre , Proteína C-Reactiva/análisis , Quimiocina CCL5 , Quimiocina CXCL1 , Quimiocina CXCL10 , Quimiocinas CC/análisis , Quimiocinas CC/genética , Quimiocinas CXC/análisis , Quimiocinas CXC/genética , Cartilla de ADN/genética , Ensayo de Inmunoadsorción Enzimática/métodos , Citometría de Flujo , Interferón gamma/análisis , Interferón gamma/genética , Interleucina-10/sangre , Interleucina-10/genética , Interleucina-1beta/análisis , Interleucina-1beta/genética , Metaloproteinasas de la Matriz/análisis , Metaloproteinasas de la Matriz/genética , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Periodontitis/patología , Periodoncio/patología , Peroxidasa/análisis , Ligando RANK/análisis , Ligando RANK/genética , Receptores CCR5/análisis , Receptores CCR5/genética , Receptores CXCR3 , Receptores de Quimiocina/análisis , Receptores de Quimiocina/genética , Receptores de Interleucina-8B/análisis , Receptores de Interleucina-8B/genética , Receptores Tipo I de Factores de Necrosis Tumoral/inmunología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Receptores Señuelo del Factor de Necrosis Tumoral/inmunología , Factor de Necrosis Tumoral alfa/inmunología

RESUMEN

The long-term persistence of pathogens in a host is a hallmark of certain infectious diseases, including schistosomiasis, leishmaniasis, and paracoccidioidomycosis (PCM). Natural regulatory T (Treg) cells are involved in control of the immune responses, including response to pathogens. Because CTLA-4 is constitutively expressed in Treg cells and it acts as a negative regulator of T cell activation in patients with PCM, here we investigated the involvement of Treg cells in the control of systemic and local immune response in patients with PCM. We found that the leukocyte subsets were similar in patients and controls, except for CD11c+CD1a+ cells. However, a higher frequency of CD4+CD25+ T cells expressing CTLA-4, glucorticoid-inducible TNFR, membrane-bound TGF-beta, and forkhead-box 3 were observed in PBMC of patients. In accordance, these cells exhibited stronger suppressive activity when compared with those from controls (94.0 vs 67.5% of inhibition of allogeneic T cell proliferation). In addition, the data showed that CD4+CD25+ T cells expressing CTLA-4+, glucocorticoid-inducible TNFR positive, CD103+, CD45RO+, membrane-bound TGF-beta, forkhead-box 3 positive, and the chemokines receptors CCR4 and CCR5 accumulate in the Paracoccidioides brasiliensis-induced lesions. Indeed, the secreted CCL17 and CCL22, both associated with the migration of Treg cells to peripheral tissues, were also detected in the biopsies. Moreover, the CD4+CD25+ T cell derived from lesions, most of them TGF-beta+, also exhibited functional activity in vitro. Altogether, these data provide the first evidence that Treg cells play a role in controlling local and systemic immune response in patients with a fungal-induced granulomatous disease advancing our understanding about the immune regulation in human chronic diseases.

Asunto(s)

Antígenos CD4/análisis , Subunidad alfa del Receptor de Interleucina-2/análisis , Paracoccidioidomicosis/inmunología , Linfocitos T Reguladores/inmunología , Antígenos CD/análisis , Antígenos de Diferenciación/análisis , Antígeno CTLA-4 , Membrana Celular/química , Membrana Celular/inmunología , Movimiento Celular , Quimiocina CCL17 , Quimiocina CCL22 , Quimiocinas/metabolismo , Quimiocinas CC/metabolismo , Enfermedad Crónica , Citocinas/metabolismo , Proteína Relacionada con TNFR Inducida por Glucocorticoide , Factor Nuclear 3-gamma del Hepatocito/análisis , Humanos , Cadenas alfa de Integrinas/análisis , Antígenos Comunes de Leucocito/análisis , Paracoccidioidomicosis/patología , Fenotipo , Receptores CCR4 , Receptores CCR5/análisis , Receptores de Quimiocina/análisis , Receptores de Factor de Crecimiento Nervioso/análisis , Receptores del Factor de Necrosis Tumoral/análisis , Factor de Crecimiento Transformador beta/análisis

RESUMEN

During helminthic infections, strong Th2 type-biased responses concomitant with impaired cell-proliferative responses to parasitic and unrelated antigens are major immunological hallmarks. Parasite glycan structures have been proposed to play a role in modulating these responses. To understand early events related to immune modulation during cestode infection, we have examined the role of intact glycans of antigens from Taenia crassiceps in the recruitment of innate cells. Soluble antigens from this cestode contained higher levels of carbohydrates than proteins. Intraperitoneal injection of the antigens rapidly recruited a cell population expressing F4/80(+)/Gr-1(+)surface markers, which adoptively suppressed naïve T-cell proliferation in vitro in response to anti-CD3/CD28 MAb stimulation in a cell-contact dependent manner. Soluble antigens with altered glycans by treatment with sodium periodate significantly reduced the recruitment of F4/80(+)/Gr1(+)cells, concomitantly their suppressive activity was abrogated, indicating that glycans have a role in the early activation of these suppressor cells. Using C3H/HeJ and STAT6-KO mice, we found that expansion and suppressive activity of F4/80(+)Gr1(+)cells induced by T. crassiceps intact antigens was TLR4 and Th2-type cytokine independent. Together with previous studies on nematode and trematode parasites, our data support the hypothesis that glycans can be involved on a similar pathway in the immunoregulation by helminths.

Asunto(s)

Antígenos Helmínticos/inmunología , Cestodos/inmunología , Infecciones por Cestodos/inmunología , Células Mieloides/inmunología , Polisacáridos/inmunología , Animales , Anticuerpos Monoclonales/inmunología , Antígenos de Diferenciación/análisis , Antígenos Helmínticos/química , Antígenos Helmínticos/aislamiento & purificación , Antígenos CD28/inmunología , Complejo CD3/inmunología , Técnicas de Cocultivo , Citocinas/inmunología , Femenino , Citometría de Flujo , Ratones , Receptores de Quimiocina/análisis , Receptor Toll-Like 4/inmunología

RESUMEN

BACKGROUND: Periapical lesions are thought to be the result of a local inflammatory response mediated by inflammatory cell infiltration and production of inflammatory mediators. Although chemokines are strongly implicated in the migration and activation of leukocytes in different inflammatory diseases and experimental models, little is known regarding the expression of chemokines and their receptors in human apical periodontitis. OBJECTIVE AND METHODS: The objective of this study was to determine the expression of chemokines and their receptors by real-time polymerase chain reaction in samples obtained from healthy gingiva, periapical granulomas, and inflammatory periradicular cysts. The inflammatory infiltrate was characterized by immunohistochemistry. RESULTS: Comparing cysts and granulomas, an increase in CD4+ and CD8+ cells was observed in granulomas, despite the similar numbers of CD45RO-positive cells detected in both lesions. The analysis of mRNA expression revealed increased levels of CCR1, CCR2, CCR3, CCR5, CXCR1, and CXCR3 in both types of lesion compared with controls. Cysts exhibited a higher expression of CCR3, CCR5, CXCR1, and CXCR3 compared to granulomas. A significantly higher expression of RANTES, IP-10, and MCP-1 was detected in cysts compared with controls or granulomas. The expression of interleukin-8, MIP-1alpha, and MIP-1beta was not different in the three experimental groups. CONCLUSIONS: The increase in Th1 type (CCR1, CCR5, and CXCR3) and Th2 type (CCR2 and CCR3) receptors in both periapical lesions suggests the concomitant occurrence of Th1 and Th2 responses. Furthermore, the prevalent expression of the receptors CCR3, CCR5, CXCR1, and CXCR3 and of the chemokines RANTES, IP-10, and MCP-1 in cysts may point to a role in the progression of granulomas to cysts.

Asunto(s)

Quimiocinas/análisis , Periodontitis Periapical/inmunología , Receptores de Quimiocina/análisis , Adulto , Anciano , Quimiocina CCL2/análisis , Quimiocina CCL3 , Quimiocina CCL4 , Quimiocina CCL5/análisis , Quimiocina CXCL10 , Quimiocinas CC/análisis , Quimiocinas CXC/análisis , Quimiotaxis de Leucocito/inmunología , Encía/inmunología , Humanos , Interleucina-8/análisis , Leucocitos/inmunología , Proteínas Inflamatorias de Macrófagos/análisis , Persona de Mediana Edad , Granuloma Periapical/inmunología , Quiste Radicular/inmunología , Receptores CCR5/análisis , Receptores del VIH/análisis , Receptores de Interleucina-8A/análisis , Linfocitos T/inmunología

RESUMEN

Current knowledge states that periodontal diseases are chronic inflammatory reactions raised in response to periodontopathogens. Many cell types and mediators, including Th1 and Th2 lymphocytes, cytokines and chemokines, appear to be involved in the immunopathogenesis of periodontal diseases. Chemokines, a family of chemotactic cytokines, bind to specific receptors and selectively attract different cell subsets to the inflammatory site. They can also interact with classical cytokines and modulate the local immune response. In order to study the role of chemokines in periodontal diseases, we examined the expression of chemokines, chemokine receptors and cytokines by means of reverse transcription-polymerase chain reaction (RT-PCR) techniques. Characteristic patterns of such factors' expression were found in gingival biopsies from patients presenting with aggressive periodontitis and chronic periodontitis. The expression of the chemokines macrophage inflammatory protein-1 alpha (MIP-1alpha) and interferon-gamma inducible protein 10 (IP-10) and of their respective receptors, CCR5 and CXCR3, were more prevalent and higher in aggressive periodontitis, and associated with higher interferon-gamma (IFN-gamma) expression and lower interleukin-10 (IL-10) expression. In contrast, chronic periodontitis patients exhibited a more frequent and higher expression of monocyte chemoattractant protein-1 (MCP-1) and its receptor CCR4, and higher expression of IL-10. It is possible that chemokines, in addition to the classical cytokines, are involved in the immunopathogenesis of periodontal disease, driving the migration and the maintenance of several inflammatory cell types such as polymorphonuclear leukocytes, dendritic cells (DCs), natural killer cells, macrophages, and subsets of lymphocytes in the gingival tissues. These cells are thought to participate in the inflammatory and immune reaction that takes place in periodontal disease, killing pathogens, presenting antigens, and producing cytokines. The selective recruitment of polarized lymphocyte subsets could result in differential cytokine production at the site of response, which is supposed to determine the stable or progressive nature of the lesion. Besides, the role of chemokines as activators and chemoattracts of osteclasts may be involved in the determination of disease severity.

Asunto(s)

Quimiocinas/análisis , Periodontitis/inmunología , Receptores de Quimiocina/análisis , Adulto , Quimiocina CCL2/análisis , Quimiocina CCL2/genética , Quimiocina CCL3 , Quimiocina CCL4 , Quimiocina CXCL10 , Quimiocinas/genética , Quimiocinas CC/inmunología , Quimiocinas CXC/análisis , Quimiocinas CXC/genética , Enfermedad Crónica , Células Dendríticas/inmunología , Femenino , Humanos , Interferón gamma/análisis , Interferón gamma/genética , Interleucina-10/análisis , Interleucina-10/genética , Células Asesinas Naturales/inmunología , Subgrupos Linfocitarios/inmunología , Proteínas Inflamatorias de Macrófagos/análisis , Proteínas Inflamatorias de Macrófagos/genética , Macrófagos/inmunología , Masculino , Persona de Mediana Edad , Neutrófilos/inmunología , Receptores CCR4 , Receptores CCR5/análisis , Receptores CCR5/genética , Receptores CXCR3 , Receptores de Quimiocina/genética , Linfocitos T/inmunología

RESUMEN

BACKGROUND: Allergic Contact Dermatitis (ACD) is regarded as a T-cell-mediated delayed-type hypersensitivity reaction. We studied the kinetics of the expression of CS-1 fibronectin, thymus and activation-regulated chemokine (CCL17/ TARC) and different chemokine receptors (CR) in skin biopsies from individuals suffering from back problems, with the antigen responsible of their contact dermatitis and an irrelevant antigen. METHODS: Samples were taken at 2, 10, and 48 hours for histological and immunohistochemical studies using monoclonal antibodies against human CS-1 fibronectin, CCL17, CD3, CD68, CD49d, CXCR3, CCR5, and CCR3. RESULTS: At positive antigen stimulated sites there was an early expression of CS-1 fibronectin (2 hours), followed by CCL17 and a later accumulation of alplha4/beta1+ (CD49d), CD3+, CD68+, CXCR3+ and CCR5+ mononuclear cells. At 48 hours, approximately 59 % of infiltrating cells were CXCR3+, 42% CCR5+, and only 14 % CCR3+. CONCLUSIONS: These results showed for the first time a very early expression of CS-1 fibronectin which preceded production of CCL17 in blood endothelial cells (BCEs) from patients' skin with ACD. The role of these molecules in recruitment of monocytes and effector T cells in ACD is discussed.

Asunto(s)

Dermatitis Alérgica por Contacto/patología , Fibronectinas/análisis , Receptores de Quimiocina/análisis , Piel/química , Piel/patología , Adulto , Anciano , Antígenos CD/análisis , Antígenos de Diferenciación Mielomonocítica/análisis , Biomarcadores/análisis , Biopsia , Complejo CD3/análisis , Quimiocina CCL17 , Quimiocinas CC/análisis , Humanos , Inmunohistoquímica , Integrina alfa4/análisis , Queratinocitos/química , Persona de Mediana Edad , Receptores CCR5/análisis , Receptores CCR6 , Receptores CXCR3