RESUMO
The increased expression of heat shock protein (Hsp)60 in different kinds of graft tissues has been associated with a proinflammatory role and rejection. However, there are very few reports in which treatment with Hsp60 delays skin allograft rejection. The aim of this work was to evaluate the capacity of encapsulated human Hsp60-derived peptide p277 to delay graft rejection in two murine models of skin transplantation with minor antigen disparities. Briefly, BALB/c mice and C57BL/6 were intranasally pre-treated with five doses of Hsp60 p277 peptide encapsulated in polylactide-co-glycolide acid microspheres (PLGM), and received skin grafts from DBA2 mice and 129/B6 (F1) mice respectively. The treatment with the peptide increased skin graft survival more than 20 days in both the mouse strains, mainly in C57BL/6 recipients (P < 0.05). Also, p277-treated BALB/c and C57BL/6 mice showed IL-10 and IFN-gamma production, induced by p277 peptide. For the first time, a mucosal schedule using the Hsp60 C-terminal peptide p277 encapsulated in PLGM showed some survival prolongation of skin grafts bearing minor antigen disparities. Our results suggest a potential role for Hsp60-based therapy and the mucosal route as a useful tool to control the inflammatory response to allografts.
Assuntos
Facilitação Imunológica de Enxerto/métodos , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/efeitos dos fármacos , Proteínas de Choque Térmico/administração & dosagem , Antígenos de Histocompatibilidade Menor/imunologia , Fragmentos de Peptídeos/administração & dosagem , Transplante de Pele/imunologia , Administração Intranasal , Animais , Chaperonina 60 , Citocinas/biossíntese , Citocinas/efeitos dos fármacos , Ensaio de Imunoadsorção Enzimática , Humanos , Ácido Láctico/administração & dosagem , Masculino , Camundongos , Microesferas , Ácido Poliglicólico/administração & dosagem , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Polímeros/administração & dosagem , Proteínas Recombinantes/administração & dosagemRESUMO
The objetive of the presented study was to determine wheter cimetidine, a type-2 histamine receptor antagonist, inhibits the immunological enhancement of allografted rats achieved by treatment with donor antigen plus anti-donor antibody. Groups of rats submitted to this active-passive enhancement protocol and treated ip with 30 (APEC30; Group I; N = 4) or 60 (APEC 60; Group II; N = 8) mg/day cimetidine for 14 days had a significantly shorter graft survival (20.2 ñ 5.1 and 11.1 ñ 2.6 days, respectively) than the control group (animals submitted to the enhancement protocol and killed on day 72 after transplant when the graft was beating normally; APE; Group III; N = 6; P<0.05). On the other hand, these animals had a significantly longer graft survival than rats allotransplanted but not treated for enhancement (ALLO; Group V; N = 5; 8.2 ñ 0.8 days). The surgical control, consisting of isotransplanted animals, had a long-term survival (ISO; Group V; N = 6; rats killed 120 days after transplant with the graft beating normally). Animals treated with cimetidine, but not submitted to the enhancement protocol (AC 60; Group IV, N = 4) had a significantly shorter graft survival (6.25 ñ 0.5) than the allotransplanted animals (Group V). These results indicate inhibition of the suppressor mechanisms which participate in this type of immunological enhancement
Assuntos
Animais , Masculino , Ratos , Cimetidina/farmacologia , Facilitação Imunológica de Enxerto/métodos , Imunização , Sobrevivência de Enxerto , Antígenos/administração & dosagem , Linfócitos/imunologia , Ratos Endogâmicos BN , Ratos Endogâmicos Lew , Transplante Homólogo/imunologiaRESUMO
The objective of the present study was to determine whether cimetidine, a type-2 histamine receptor antagonist, inhibits the immunological enhancement of allografted rats achieved by treatment with donor antigen plus anti-donor antibody. Groups of rats submitted to this active-passive enhancement protocol and treated ip with 30 (APEC 30; Group I; N = 4) or 60 (APEC 60; Group II; N = 8) mg/day cimetidine for 14 days had a significantly shorter graft survival (20.2 +/- 5.1 and 11.1 +/- 2.6 days, respectively) than the control group (animals submitted to the enhancement protocol and killed on day 72 after transplant when the graft was beating normally; APE; Group III; N = 6; P less than 0.05). On the other hand, these animals had a significantly longer graft survival than rats allotransplanted but not treated for enhancement (ALLO; Group V; N = 5; 8.2 +/- 0.8 days). The surgical control, consisting of isotransplanted animals, had a long-term survival (ISO; Group VI; N = 6; rats killed 120 days after transplant with the graft beating normally). Animals treated with cimetidine, but not submitted to the enhancement protocol (AC 60; Group IV, N = 4) had a significantly shorter graft survival (6.25 +/- 0.5) than the allotransplanted animals (Group V). These results indicate inhibition of the suppressor mechanisms which participate in this type of immunological enhancement.