The role of complement in the pathogenesis of renal ischemia-reperfusion injury and fibrosis.
The complement system is a major component of innate immunity and has been commonly identified as a central element in host defense, clearance of immune complexes, and tissue homeostasis. After ischemia-reperfusion injury (IRI), the complement system is activated by endogenous ligands that trigger proteolytic cleavage of complement components via the classical, lectin and/or alternative pathway. The result is the formation of terminal complement components C3a, C5a, and the membrane attack complex (C5b-9 or MAC), all of which play pivotal roles in the amplification of the inflammatory response, chemotaxis, neutrophil/monocyte recruitment and activation, and direct tubular cell injury. However, recent evidence suggests that complement activity transcends innate host defense and there is increasing data suggesting complement as a regulator in processes such as allo-immunity, stem cell differentiation, tissue repair, and progression to fibrosis. In this review, we discuss recent advances addressing the role of complement as a regulator of IRI and renal fibrosis after organ donation for transplantation. We will also briefly discuss currently approved therapies that target complement activity in kidney ischemia-reperfusion and transplantation.
Department of Surgery, Division of Transplantation, University of Wisconsin-Madison School of Medicine and Public Health, H4/782 Clinical Science Center, 600 Highland Avenue, 53792 Madison, WI, USA.
Juan S
JS
Danobeitia
Department of Medicine, Division of Nephrology, University of Wisconsin- Madison School of Medicine and Public Health, UW Medical Foundation Centennial Building, 1685 Highland Avenue, 53705 Madison, WI, USA.
Arjang
A
Djamali
Department of Surgery, Division of Transplantation, University of Wisconsin-Madison School of Medicine and Public Health, H4/782 Clinical Science Center, 600 Highland Avenue, 53792 Madison, WI, USA.
Luis A
LA
Fernandez