The TIM-1:TIM-4 pathway enhances renal ischemia-reperfusion injury.
J Am Soc Nephrol
; 22(3): 484-95, 2011 Mar.
Article
en En
| MEDLINE
| ID: mdl-21355054
ABSTRACT
CD4+ T cells contribute to the pathogenesis of ischemia-reperfusion injury, which is the primary cause of delayed graft failure after kidney transplantation. The TIM-1TIM-4 pathway participates in the activation/differentiation of CD4+ T cells, suggesting that it may modulate ischemia-reperfusion injury. Here, we studied the role of TIM-1 in a murine uninephrectomized renal ischemia-reperfusion injury model. Blocking the TIM-1TIM-4 pathway with an antagonistic monoclonal antibody protected renal function and diminished reperfusion injury resulting from 30 minutes of ischemia. Histologic examination showed significantly less evidence of renal damage as evidenced by diminished tubular necrosis, preservation of the brush border, fewer cast formations, and less tubular dilation. Blocking TIM-1 also reduced the number of apoptotic cells and diminished local inflammation within ischemic kidneys, the latter shown by decreased recruitment of macrophages, neutrophils, and CD4+ T cells and by reduced local production of proinflammatory cytokines. Furthermore, TIM-1 blockade significantly improved survival after ischemia-reperfusion injury. Taken together, these data suggest that the TIM-1TIM-4 pathway enhances injury after renal ischemia-reperfusion injury and may be a therapeutic target.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Daño por Reperfusión
/
Transducción de Señal
/
Riñón
/
Proteínas de la Membrana
Límite:
Animals
Idioma:
En
Año:
2011
Tipo del documento:
Article