C3a Is Required for the Production of CXC Chemokines by Tubular Epithelial Cells after Renal Ishemia/Reperfusion

摘要: The complement system is one of the major ways by which body detects injury to self cells, and alternative pathway rapidly activated within tubulointerstitium after renal ischemia/reperfusion (I/R). In current study, we investigate hypothesis that recognition tubular a mechanism systemic inflammatory response initiated. Gene array analysis mouse kidney following I/R initially identified MIP-2 (CXCL2) keratinocyte-derived chemokine (KC or CXCL1) as factors are produced in complement-dependent fashion. Using situ hybridization, next demonstrated these expressed epithelial cells postischemic kidneys. Mouse proximal (PTECs) culture were then exposed an intact found produce both chemokines. Selective antagonism C3a receptor significantly attenuated production KC PTECs, whereas C5a prevention membrane attack complex (MAC) formation did not have significant effect. Treatment PTECs with NF-kappaB inhibitor also prevented full expression pathway. summary, activation induces PTECs. This innate immune thereby recognizes hypoxic triggers through generation subsequent system.