Open AccessLack of a Functional Alternative Complement Pathway Ameliorates Ischemic Acute Renal Failure in Mice
Author(s) -
Joshua M. Thurman,
Danica Galešić Ljubanović,
Charles L. Edelstein,
Gary S. Gilkeson,
V. Michael Holers
Publication year - 2003
Publication title -
the journal of immunology/the journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.737
H-Index - 372
eISSN - 1550-6606
pISSN - 0022-1767
DOI - 10.4049/jimmunol.170.3.1517
Subject(s) - alternative complement pathway , complement system , pathogenesis , kidney , complement factor b , acute kidney injury , ischemia , medicine , renal ischemia , renal function , classical complement pathway , renal medulla , medulla , immunology , infiltration (hvac) , biology , reperfusion injury , immune system , physics , thermodynamics
Ischemia/reperfusion (I/R) injury of the kidney is a common cause of acute renal failure (ARF) and is associated with high morbidity and mortality in the intensive care unit. The mechanisms underlying I/R injury are complex. Studies have shown that complement activation contributes to the pathogenesis of I/R injury in the kidney, but the exact mechanisms of complement activation have not been defined. We hypothesized that complement activation in this setting occurs via the alternative pathway and that mice deficient in complement factor B, an essential component of the alternative pathway, would be protected from ischemic ARF. Wild-type mice suffered from a decline in renal function and had significant tubular injury, particularly in the outer medulla, after I/R. We found that factor B-deficient mice (fB(-/-)) developed substantially less functional and morphologic renal injury after I/R. Furthermore, control wild-type mice had an increase in tubulointerstitial complement C3 deposition and neutrophil infiltration in the outer medulla after I/R, whereas fB(-/-) mice demonstrated virtually no C3 deposition or neutrophil infiltration. Our results demonstrate that complement activation in the kidney after I/R occurs exclusively via the alternative pathway, and that selective inhibition of this pathway provides protection to the kidneys from ischemic ARF.