RESUMEN
Brain death is characterized by a generalized inflammatory response that results in multiorgan damage. This process is mainly mediated through cytokines, which amplify graft immunogenicity. We investigated the immunological response in a brain death liver donor model and analysed the effects of thalidomide, a drug with powerful immunomodulatory properties. Brain death was induced in male Lewis rats. We studied three groups: Control (sham-operated rats in which trepanation was performed without inserting the balloon catheter), BD (rats subjected to brain death by increasing intracranial pressure) and BD + Thalid (BD rats receiving thalidomide after brain death). After 6 h, serum levels of AST, ALT, LDH, and ALP as well as systemic and hepatic levels of TNF-α, IL1-ß, IL-6, and IL-10 were analysed. We also determined the mRNA expression of MHC Class I and Class II, NF-κB, and macrophage infiltration. NF-κB was also examined by electrophoretic mobility shift assay. Thalidomide treatment significantly reduced serum levels of hepatic enzymes and TNF-α, IL-1-ß, and IL-6. These cytokines were evaluated at either the mRNA expression or protein level in liver tissue. In addition, thalidomide administration resulted in a significant reduction in macrophages, MHC Class I and Class II, and NF-κB activation. This study reveals that thalidomide significantly inhibited the immunologic response and graft immunogenicity, possibly through suppression of NF-κB activation.
Asunto(s)
Muerte Encefálica/inmunología , Rechazo de Injerto/prevención & control , Trasplante de Hígado/efectos adversos , Talidomida/administración & dosificación , Recolección de Tejidos y Órganos/métodos , Aloinjertos/efectos de los fármacos , Aloinjertos/inmunología , Animales , Modelos Animales de Enfermedad , Rechazo de Injerto/inmunología , Humanos , Hígado/efectos de los fármacos , Hígado/inmunología , Trasplante de Hígado/métodos , Masculino , Ratas , Ratas Endogámicas LewRESUMEN
BACKGROUND AND OBJECTIVES: In patients with kidney failure due to IgA nephropathy, IgA deposits can recur in a subsequent kidney transplant. The incidence, effect, and risk factors of IgA nephropathy recurrence is unclear, because most studies have been single center and sample sizes are relatively small. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We performed a multicenter, international, retrospective study to determine the incidence, risk factors, and treatment response of recurrent IgA nephropathy after kidney transplantation. Data were collected from all consecutive patients with biopsy-proven IgA nephropathy transplanted between 2005 and 2015, across 16 "The Post-Transplant Glomerular Disease" study centers in Europe, North America, and South America. RESULTS: Out of 504 transplant recipients with IgA nephropathy, recurrent IgA deposits were identified by kidney biopsy in 82 patients; cumulative incidence of recurrence was 23% at 15 years (95% confidence interval, 14 to 34). Multivariable Cox regression revealed a higher risk for recurrence of IgA deposits in patients with a pre-emptive kidney transplant (hazard ratio, 3.45; 95% confidence interval, 1.31 to 9.17) and in patients with preformed donor-specific antibodies (hazard ratio, 2.59; 95% confidence interval, 1.09 to 6.19). After kidney transplantation, development of de novo donor-specific antibodies was associated with subsequent higher risk of recurrence of IgA nephropathy (hazard ratio, 6.65; 95% confidence interval, 3.33 to 13.27). Immunosuppressive regimen was not associated with recurrent IgA nephropathy in multivariable analysis, including steroid use. Graft loss was higher in patients with recurrence of IgA nephropathy compared with patients without (hazard ratio, 3.69; 95% confidence interval, 2.04 to 6.66), resulting in 32% (95% confidence interval, 50 to 82) graft loss at 8 years after diagnosis of recurrence. CONCLUSIONS: In our international cohort, cumulative risk of IgA nephropathy recurrence increased after transplant and was associated with a 3.7-fold greater risk of graft loss.
Asunto(s)
Anticuerpos/sangre , Glomerulonefritis por IGA/epidemiología , Fallo Renal Crónico/etiología , Fallo Renal Crónico/cirugía , Adulto , Aloinjertos/inmunología , Aloinjertos/patología , Biopsia , Brasil/epidemiología , Europa (Continente)/epidemiología , Femenino , Glomerulonefritis por IGA/complicaciones , Glomerulonefritis por IGA/tratamiento farmacológico , Glomerulonefritis por IGA/patología , Supervivencia de Injerto , Humanos , Incidencia , Riñón/patología , Trasplante de Riñón , Masculino , Persona de Mediana Edad , Recurrencia , Estudios Retrospectivos , Factores de Riesgo , Estados Unidos/epidemiologíaRESUMEN
Germ cell transplantation and testis graft represent promising biotechnologies that can be applied for the reproduction of commercial or endangered species. However, mechanisms of rejection from the host immune system might remove the transplanted donor cells/tissues and limit the surrogate production of gametes. In this work, we administered emulsion containing-immunosuppressants to verify whether they are capable to prevent immune rejection and promote survival of testis allografts in rainbow trout. In the first part of this study, we demonstrated in vitro that tacrolimus and cyclosporine were able to affect viability, inhibit leucocyte proliferation, and suppress il2 expression in vitro. In in vivo experiments, both doses of tacrolimus (0.5 and 1.5 mg/kg) and the lower dose of cyclosporine (20 mg/kg) significantly inhibited the expression of il2 in head kidney, three days post-injection. A higher dose of cyclosporine (40 mg/kg) was able to inhibit il2 expression for up to seven days post-injection. In the second part, testis allografts were conducted in fish treated weekly with emulsion containing-tacrolimus. Immunohistochemical, conventional histology, and qRT-PCR (vasa) analysis demonstrated the presence of spermatogonial cells by the fifth week, in animals treated with 0.5 mg/kg of tacrolimus similar as found in autografted group. In the group treated with the highest tacrolimus dose (1.5 mg/kg) and in the non-treated group (without immunosuppressant), no germ cells or their respective markers were detected. il2 expression in head kidney was also suppressed in grafted animals treated with tacrolimus compared to non-treated group. These results suggest that tacrolimus may be a promising immunosuppressant for testis allografts or germ cell transplantation in rainbow trout. Co-administration combining tacrolimus (at lower dose) with other immunosuppressive drugs for inhibiting other activation pathways of the immune system, as performed in human organ transplantation, could be an alternative approach to optimize the immunosuppressive effects in host organisms.
Asunto(s)
Aloinjertos/inmunología , Ciclosporina/farmacología , Inmunosupresores/farmacología , Oncorhynchus mykiss/cirugía , Espermatogonias/inmunología , Tacrolimus/farmacología , Testículo/trasplante , Trasplante Homólogo/veterinaria , Animales , MasculinoRESUMEN
Cytokine polymorphisms can influence their plasma levels and thus affect the immune response in renal transplantation. A total of 146 renal transplant recipients (RTR) were classified into groups according to the estimated glomerular filtration rate (R1: < 60 and R2: ≥ 60 mL/min/1.73 m2) and time after transplantation (T1: 1 to 24, T2: 25 to 60, T3: 61 to 120, and T4: > 120 months after transplantation). The polymorphisms were genotyped by single specific primer-polymerase chain reaction. IL-10 was measured by ELISA and IL-6, and TNF levels were determined using Miliplex®. A higher frequency of the - 308G allele and the - 308G/G genotype, low-producer, was observed in the R1 group compared with R2. In addition, a higher frequency of the - 308A carriers, high-producer, was found in the R2 group. However, no significant difference was observed in cytokine levels when both groups were compared. Higher levels of IL-6 were observed in T1 compared with T2 and T4 groups. Lower IL-6 levels were found in T2 compared with T3 group. Lower levels of IL-10 were also found in T1 group in relation to T2, while higher levels of this cytokine were observed in T2 group compared with T3. The results suggest that the - 308G > A polymorphism in the TNF gene is associated with filtration function after renal transplantation, and IL-6 and IL-10 levels change according to the time after transplantation. Thus, the joint evaluation of - 308G > A polymorphism in TNF gene and IL-6 and IL-10 levels would provide a broader and effective view on the clinical monitoring of RTR.
Asunto(s)
Rechazo de Injerto/diagnóstico , Interleucina-10/sangre , Interleucina-6/sangre , Trasplante de Riñón/efectos adversos , Factor de Necrosis Tumoral alfa/genética , Adulto , Alelos , Aloinjertos/inmunología , Aloinjertos/fisiopatología , Biomarcadores/sangre , Brasil , Femenino , Frecuencia de los Genes , Tasa de Filtración Glomerular/fisiología , Rechazo de Injerto/sangre , Rechazo de Injerto/genética , Rechazo de Injerto/inmunología , Humanos , Interleucina-10/genética , Interleucina-6/genética , Riñón/inmunología , Riñón/fisiopatología , Fallo Renal Crónico/cirugía , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Periodo Posoperatorio , Factores de Tiempo , Factor de Necrosis Tumoral alfa/sangreRESUMEN
Bone grafting is important to preserve the alveolar bone ridge height and volume for dental implant placement. Even though implant-supported overdentures present highly successful outcomes, it seems that a great number of edentulous individuals have not pursued implant-based rehabilitation. The cost of the treatment is one of the reasons of discrepancy between highly successful therapy and its acceptance. Therefore, the development of biomaterials for bone grafting with comparable characteristics and biological effects than those renowned internationally, is necessary. In addition, domestic manufacture would reduce the high costs in public health arising from the application of these biomaterials in the dental feld. The purpose of this clinical case report is to provide preliminary clinical evidence of the efficacy of a new bovine bone graft in the bone healing process when used for sinus floor elevation. (AU)
El uso de injertos óseos es importante para preservar la altura y el volumen de la cresta alveolar para la colocación de implantes dentales. Si bien las sobredentaduras implanto-soportadas presentan resultados altamente exitosos, la mayoría de las personas desdentadas no han sido rehabilitadas mediante implantes dentales. Uno de los principales motivos por los cuales los pacientes no aceptan este tipo de tratamiento, altamente exitoso, es el elevado costo del mismo. Por ello, es necesario el desarrollo de biomateriales de injerto óseo con características y efectos biológicos comparables a los reconocidos internacionalmente. Asimismo, la fabricación nacional reduciría los altos costos en Salud Pública derivados de la aplicación de estos biomateriales en el campo dental. El objetivo de esta comunicación es presentar un caso clínico a fin de proporcionar evidencia preliminar acerca de la eficacia de un nuevo injerto de hueso bovino en el proceso de cicatrización ósea en el levantamiento del piso del seno maxilar. (AU)
Asunto(s)
Humanos , Animales , Femenino , Persona de Mediana Edad , Bovinos , Ratas , Trasplante Óseo/métodos , Arcada Parcialmente Edéntula/rehabilitación , Elevación del Piso del Seno Maxilar/métodos , Osteogénesis , Argentina , Materiales Biocompatibles , Bovinos/fisiología , Carticaína/administración & dosificación , Clorhexidina/administración & dosificación , Naproxeno/administración & dosificación , Salud Pública/economía , Oseointegración , Dentaduras , Trasplante Óseo/tendencias , Arcada Parcialmente Edéntula/patología , Arcada Parcialmente Edéntula/terapia , Durapatita/uso terapéutico , Combinación Amoxicilina-Clavulanato de Potasio/administración & dosificación , Implantación Dental Endoósea/métodos , Elevación del Piso del Seno Maxilar/tendencias , Aloinjertos/inmunología , Aloinjertos/trasplanteRESUMEN
INTRODUCTION: The complex interaction between cytomegalovirus (CMV) infection and acute rejection after kidney transplantation is well recognized. METHODS: This single center retrospective cohort analysis investigated the incidence and risk factors associated with CMV infection after treatment for acute rejection (tAR) in kidney transplant recipients receiving only CMV preemptive therapy. Of the 938 kidney transplants performed between 04/30/2014 and 04/30/2015 we identified 87 (9.3%) that were treated for acute rejection within the first year. RESULTS: Most patients (64%) received rATG induction therapy followed by tacrolimus in combination with azathioprine (67%) or mycophenolate (33%) and corticosteroids. The incidence of CMV infection/disease after tAR was 47%, of which 73% occurred within 30 days. Using multivariable logistic regression analysis, eGFR at 1 month (OR = 0.98; 95% CI, 0.97-0.99; P = 0.007) and timing of tAR (OR = 0.98; 95% CI, 0.96-0.99; P = 0.021) were independently associated with CMV infection/disease after tAR. CONCLUSION: In this cohort of kidney transplant recipients receiving tacrolimus-based immunosuppressive and preemptive CMV therapy, almost 50% developed CMV infection/disease after tARin the first year of transplantation. Early rejection and poor initial renal function were risk factors associated with CMV infection or disease.
Asunto(s)
Infecciones por Citomegalovirus/epidemiología , Citomegalovirus/inmunología , Rechazo de Injerto/tratamiento farmacológico , Inmunosupresores/efectos adversos , Trasplante de Riñón/efectos adversos , Adulto , Anciano , Aloinjertos/efectos de los fármacos , Aloinjertos/inmunología , Aloinjertos/fisiopatología , Profilaxis Antibiótica/métodos , Suero Antilinfocítico/administración & dosificación , Suero Antilinfocítico/efectos adversos , Antivirales/uso terapéutico , Azatioprina/administración & dosificación , Azatioprina/efectos adversos , Citomegalovirus/aislamiento & purificación , Infecciones por Citomegalovirus/inmunología , Infecciones por Citomegalovirus/virología , Quimioterapia Combinada/métodos , Femenino , Tasa de Filtración Glomerular/efectos de los fármacos , Tasa de Filtración Glomerular/fisiología , Rechazo de Injerto/inmunología , Humanos , Inmunosupresores/administración & dosificación , Incidencia , Riñón/efectos de los fármacos , Riñón/inmunología , Riñón/fisiopatología , Masculino , Persona de Mediana Edad , Ácido Micofenólico/administración & dosificación , Ácido Micofenólico/efectos adversos , Estudios Retrospectivos , Factores de Riesgo , Tacrolimus/administración & dosificación , Tacrolimus/efectos adversos , Adulto JovenRESUMEN
BACKGROUND: Belatacept could be the treatment of choice in renal-transplant recipients with renal dysfunction attributed to calcineurin inhibitor (CNI) nephrotoxicity. Few studies have described its use in patients with donor-specific antibody (DSA). METHODS: We retrospectively evaluated conversion from CNIs to belatacept in 29 human leukocyte antigen-immunized renal-transplant recipients. Data about acute rejection, DSA, and renal function were collected. These patients were compared with 42 nonimmunized patients treated with belatacept. RESULTS: Patients were converted from CNIs to belatacept a median of 444 days (interquartile range, 85-1200) after transplantation and were followed up after belatacept conversion, for a median of 308 days (interquartile range, 125-511). At conversion, 16 patients had DSA. Nineteen DSA were observed in these 16 patients, of which 11/19 were <1000 mean fluorescence intensity (MFI), 7/19 were between 1000 and 3000 MFI, and one was >3000 MFI. At last follow-up, preexisting DSA had decreased or stabilized. Seven patients still had DSA with a mean MFI of 1298 ± 930 at the last follow-up. No patient developed a de novo DSA in the DSA-positive group. In the nonimmunized group, one patient developed de novo DSA (A24-MFI 970; biopsy for cause did not show biopsy-proven acute rejection or microinflammation score). After belatacept conversion, one antibody-mediated rejection was diagnosed. The mean estimated glomerular filtration rate improved from 31.7 ± 14.2 mL/min/1.73 m to 40.7 ± 12.3 mL/min/1.73 m (P < 0.0001) at 12 months after conversion. We did not find any significant difference between groups in terms of renal function, proteinuria, or biopsy-proven acute rejection. CONCLUSIONS: We report on a safe conversion to belatacept in human leukocyte antigen-immunized patients with low DSA levels.
Asunto(s)
Abatacept/administración & dosificación , Inhibidores de la Calcineurina/efectos adversos , Rechazo de Injerto/tratamiento farmacológico , Isoanticuerpos/sangre , Trasplante de Riñón/efectos adversos , Insuficiencia Renal/prevención & control , Adulto , Anciano , Aloinjertos/efectos de los fármacos , Aloinjertos/inmunología , Aloinjertos/patología , Biopsia , Inhibidores de la Calcineurina/administración & dosificación , Sustitución de Medicamentos , Femenino , Tasa de Filtración Glomerular/efectos de los fármacos , Tasa de Filtración Glomerular/inmunología , Rechazo de Injerto/sangre , Rechazo de Injerto/inmunología , Rechazo de Injerto/patología , Antígenos HLA/inmunología , Humanos , Isoanticuerpos/inmunología , Isoantígenos/inmunología , Riñón/efectos de los fármacos , Riñón/inmunología , Riñón/patología , Masculino , Persona de Mediana Edad , Insuficiencia Renal/inducido químicamente , Resultado del TratamientoAsunto(s)
Aloinjertos/patología , Enfermedad Hepática en Estado Terminal/cirugía , Rechazo de Injerto/patología , Trasplante de Hígado/efectos adversos , Hígado/patología , Aloinjertos/inmunología , Biomarcadores/sangre , Biopsia , Enfermedad Hepática en Estado Terminal/mortalidad , Enfermedad Hepática en Estado Terminal/patología , Rechazo de Injerto/diagnóstico , Rechazo de Injerto/inmunología , Rechazo de Injerto/prevención & control , Supervivencia de Injerto/inmunología , Humanos , Terapia de Inmunosupresión/métodos , Hígado/inmunología , Recurrencia , Índice de Severidad de la Enfermedad , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: This analysis compared efficacy, renal function, and histology in kidney transplant recipients receiving tacrolimus (TAC) combined with everolimus (EVR) or mycophenolate (MPS). METHODS: This was a retrospective analysis from a randomized trial in kidney transplant recipients who received a single 3 mg/kg dose of rabbit antithymocyte globulin (r-ATG), TAC, EVR, and prednisone (PRED; r-ATG/EVR, n = 85), basiliximab (BAS), TAC, EVR, and PRED (BAS/EVR, n = 102) or BAS, TAC, MPS, and PRED (BAS/MPS, n = 101). We evaluated the incidence of de novo donor-specific anti-human leukocyte antigens antibodies (DSA) and histology on protocol biopsies at 12 months, and the incidence of acute rejection, estimated glomerular filtration rate (eGFR) and proteinuria at 36 months. RESULTS: At 12 months, there were no differences in de novo DSA (6.4 vs. 3.4 vs. 5.5%) or in subclinical inflammation (2.0 vs. 4.8 vs. 10.2%), interstitial fibrosis/tubular atrophy (57.1 vs. 58.5 vs. 53.8%) and C4d deposition (2.0 vs. 7.3 vs. 2.6%). At 36 months, there were no differences in the incidence of treatment failure (19.0 vs. 27.7 vs. 27.7%, p = 0.186), first biopsy-proven acute rejection (9.5 vs. 21.8 vs. 16.8%, p = 0.073), and urine protein/creatinine ratios (0.53 ± 1.05 vs. 0.62 ± 0.75 vs. 0.71 ± 1.24). eGFR was lower in the BAS/EVR compared to that in the BAS/MPS group (53.4 ± 20.9 vs. 50.8 ± 19.5 vs. 60.7 ± 21.2 mL/min/1.73 m2, p = 0.017) but comparable using a sensitive analysis (49.5 ± 23 vs. 47.5 ± 22.6 vs. 53.6 ± 27.8 mL/min/1.73 m2, p = 0.207). CONCLUSION: In this cohort, the use of EVR and reduced TAC concentrations were associated with comparable efficacy, renal function, and histological parameters compared to the standard-of-care immunosuppressive regimen.
Asunto(s)
Rechazo de Injerto/prevención & control , Supervivencia de Injerto/efectos de los fármacos , Antígenos HLA/inmunología , Inmunosupresores/uso terapéutico , Fallo Renal Crónico/terapia , Trasplante de Riñón/efectos adversos , Adulto , Aloinjertos/inmunología , Aloinjertos/patología , Anticuerpos Monoclonales/uso terapéutico , Suero Antilinfocítico/uso terapéutico , Basiliximab , Biopsia , Quimioterapia Combinada/métodos , Everolimus/uso terapéutico , Femenino , Tasa de Filtración Glomerular , Rechazo de Injerto/epidemiología , Rechazo de Injerto/inmunología , Rechazo de Injerto/patología , Humanos , Riñón/inmunología , Riñón/patología , Pruebas de Función Renal , Masculino , Persona de Mediana Edad , Ácido Micofenólico/uso terapéutico , Prednisona/uso terapéutico , Estudios Prospectivos , Proteínas Recombinantes de Fusión/uso terapéutico , Estudios Retrospectivos , Tacrolimus/uso terapéutico , Donantes de Tejidos , Insuficiencia del Tratamiento , Resultado del Tratamiento , Privación de Tratamiento/estadística & datos numéricos , Adulto JovenRESUMEN
Increasing evidence indicates the existence of a complex cross-regulation between the most important biosensors of the human body: The immune and nervous systems. Cytokines control body temperature and trigger autoimmune disorders in the central nervous system, whereas neuropeptides released in peripheral tissues and lymphoid organs modulate inflammatory (innate) and adaptive immune responses. Surprisingly, the effects of nerve fibers and the antidromic release of its pro-inflammatory neuropeptides on the leukocytes of the immune system that mediate graft rejection are practically unknown. In the transplantation field, such area of research remains practically unexplored. A recent study by Riol-Blanco et al has revealed new details on how nociceptive nerves regulate the pro-inflammatory function of leukocytes in peripheral tissues. Although the mechanism(s) by which neuroinflammation affects the immune response against the allograft remains unknown, recent data suggest that this new area of research is worth exploring for potential development of novel complementary therapies for prevention/treatment of graft rejection.
Asunto(s)
Investigación Biomédica/tendencias , Sistema Inmunológico/fisiología , Nociceptores/fisiología , Trasplante de Órganos , Aloinjertos/inmunología , Aloinjertos/fisiología , Animales , Citocinas/fisiología , Rechazo de Injerto/fisiopatología , Rechazo de Injerto/prevención & control , Humanos , Modelos AnimalesRESUMEN
Retinoic acid (RA), a vitamin A metabolite, has been attributed to relevant functions in adaptive immunity. On T cells, the disruption on RA signaling alters both CD4+ and CD8+ T cells effector function. In this study, we evaluated the contribution of RA synthesis during the immune response using an in vivo skin transplantation model. Our data indicates that the frequency and number of cells containing an active retinaldehyde dehydrogenase (RALDH), a key enzyme for RA synthesis, is increased during skin transplant rejection. In addition, we found that the expression of the mRNA coding for the isoform RALDH2 is up-regulated on graft rejecting draining lymph nodes (dLNs) cells. Lastly, we observed that IFN-γ and IL-17 production by ex vivo re-stimulated dLNs cells is greatly increased during rejection, which it turns depends on RA synthesis, as shown in experiments using a specific RALDH inhibitor. Altogether, our data demonstrate that RA synthesis is incremented during the immune response against an allograft, and also indicates that the synthesis of RA is required for cytokine production by dLNs resident T cells.
Asunto(s)
Aloinjertos/inmunología , Citocinas/biosíntesis , Rechazo de Injerto/inmunología , Retinal-Deshidrogenasa/metabolismo , Células TH1/inmunología , Células TH1/metabolismo , Células Th17/inmunología , Células Th17/metabolismo , Aloinjertos/metabolismo , Animales , Activación Enzimática , Expresión Génica , Rechazo de Injerto/genética , Ratones , Modelos Animales , Retinal-Deshidrogenasa/genética , Trasplante de Piel , Trasplante Homólogo , Tretinoina/metabolismoRESUMEN
During allograft rejection, several immune cell types, including dendritic cells, CD4(+) and CD8(+) T cells among others, recirculate between the graft and the nearest draining lymph node, resulting in immunity against the 'foreign' tissue. Regulatory CD4(+) T cells are critical for controlling the magnitude of the immune response and may act to promote or maintain tolerance. They are characterized by the expression of CD25 and Foxp3, and more recently, Neuropilin-1 (Nrp1). The role of these suppressor cells during allograft rejection is not well understood. Our work shows that during graft rejection, there is an increase in the frequency of total CD4(+) T cells expressing Nrp1, but the expression of this molecule is downregulated in the regulatory CD4(+) T-cell compartment. Interestingly, the expression of the transcription factor Eos, which renders cell function stability, is also reduced. In adoptive transfer experiments, we observed that during allograft rejection: (i) natural regulatory CD4(+) T cells maintain high levels of Nrp1 expression, (ii) effector CD4(+) T cells (Nrp1(-)) become Nrp1(+)Eos(+) and (iii) the transfer of regulatory CD4(+) T cells (Nrp1(+)) can promote allograft survival, and also enhance the gain of Nrp1 and Eos on T-effector cells. Together, these data suggest that rejection occurs, at least in part, through the loss of Nrp1 expression on regulatory CD4(+) T cells, their stability or both. Additionally, the transfer of regulatory CD4(+) T cells (based on Nrp1 expression) permits the acceptance of the allograft, placing Nrp1 as a new target for immune therapy.
Asunto(s)
Aloinjertos/inmunología , Supervivencia de Injerto/inmunología , Neuropilina-1/metabolismo , Trasplante de Piel , Linfocitos T Reguladores/inmunología , Animales , Proteínas Portadoras/metabolismo , Proteínas de Unión al ADN , Regulación hacia Abajo , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Proteínas del Tejido Nervioso/metabolismo , Fenotipo , Linfocitos T Reguladores/metabolismoRESUMEN
OBJECTIVE: To elucidate the role of the spleen and splenic allograft in lipid control and evaluate its effect on the lipid profile of rats. METHOD: 32 male Wistar rats were randomly assigned into four groups: control group (1), total splenectomy group (2), splenectomy and implantation of allograft group (3) and double spleen group (4). Each group was subdivided into two subgroups: A and B, based on the death of the animals after 30 or 120 days of monitoring. The procedures in groups 2, 3 and 4 were made simultaneously, and splenectomized animals, groups 2 and 3 were donors, respectively, for the animals of groups 3 and 4. In group 4 the spleen was preserved and the animals received implants from the spleens of rats from group 3. The regeneration of splenic tissue was evaluated by macroscopic and microscopic analyzes of the grafts and own spleens, as well as with measurements of VLDL, HDL, LDL, total cholesterol and triglycerides. RESULTS: after 120 days, Group 4 showed levels of total cholesterol and LDL lower than the other groups. Group 1 had higher levels of lipids. CONCLUSION: The technique of double spleen was effective in the control of lipid metabolism, corroborating the function of the spleen as a reserve of lipids.
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Aloinjertos/inmunología , Aloinjertos/metabolismo , Colesterol/metabolismo , Bazo/inmunología , Bazo/metabolismo , Triglicéridos/metabolismo , Animales , Masculino , Distribución Aleatoria , Ratas , Ratas Wistar , Bazo/trasplante , EsplenectomíaRESUMEN
OBJECTIVE: To elucidate the role of the spleen and splenic allograft in lipid control and evaluate its effect on the lipid profile of rats. METHOD: 32 male Wistar rats were randomly assigned into four groups: control group (1), total splenectomy group (2), splenectomy and implantation of allograft group (3) and double spleen group (4). Each group was subdivided into two subgroups: A and B, based on the death of the animals after 30 or 120 days of monitoring. The procedures in groups 2, 3 and 4 were made simultaneously, and splenectomized animals, groups 2 and 3 were donors, respectively, for the animals of groups 3 and 4. In group 4 the spleen was preserved and the animals received implants from the spleens of rats from group 3. The regeneration of splenic tissue was evaluated by macroscopic and microscopic analyzes of the grafts and own spleens, as well as with measurements of VLDL, HDL, LDL, total cholesterol and triglycerides. RESULTS: after 120 days, Group 4 showed levels of total cholesterol and LDL lower than the other groups. Group 1 had higher levels of lipids. CONCLUSION: The technique of double spleen was effective in the control of lipid metabolism, corroborating the function of the spleen as a reserve of lipids. .
OBJETIVO: Este estudo objetiva elucidar o papel do baço e do aloenxerto esplênico no controle lipídico e avaliar seu efeito no lipidograma de ratos. MÉTODO: Foram distribuídos aleatoriamente 32 ratos machos da linhagem Wistar em quatro grupos: grupo controle (1), grupo esplenectomia total (2), grupo esplenectomia e implante de aloenxerto (3) e grupo baço duplo (4). Cada grupo foi subdividido em dois subgrupos: A e B, com base na morte dos animais após 30 ou 120 dias de acompanhamento. Os procedimentos nos animais dos grupos 2, 3 e 4 foram feitos simultaneamente, sendo que os animais esplenectomizados, grupos 2 e 3, foram doadores, respectivamente, para os animais dos grupos 3 e 4. No grupo 4 preservou-se o baço dos animais e implantou-se outro baço oriundo dos ratos do grupo 3. A regeneração do tecido esplênico foi avaliada por análises macro e microscópicas dos enxertos e dos baço próprios, bem como dosagens de VLDL, HDL, LDL, colesterol total e triglicérides. RESULTADOS: O Grupo 4 apresentou, após 120 dias, níveis de LDL e colesterol total inferiores aos demais grupos. O Grupo 1 apresentou os níveis de lipidograma mais elevados. CONCLUSÃO: A técnica do baço duplo foi eficaz no controle do metabolismo lipídico, comprovando a função do baço como reserva de lipídios. .