ACTIVATION OF THE TERMINAL COMPLEMENT CASCADE IN RENAL INFARCTION

Ischemic injury is an important cause of functional derangement in the kidney. The complement (C) system has previously been shown to be an important mediator of ischemic tissue injury in myocardial infarction. In the present study we therefore investigated the possible role of C in renal ischemic lesions. The deposition and distribution of various C components (C1q, C3c, C3d, C4, C5, C6, C9) and regulators [vitronec tin, clusterin and protectin (CD59)] in human renal infarction lesions were studied by indirect immunofluorescence microscopy. Deposition of components of the terminal C complex (TCC), as well as vitronectin an d clusterin, were observed throughout the infarcted areas. The stronge st deposits were seen on the membranes of tubular epithelial cells and in the tubular lumina of the infarction areas, especially in the bord er zone between normal and infarcted tissue. Using markers for differe nt segments of tubuli (Tamm-Horsfall glycoprotein and brush border ant igens) it was possible to localize deposits of TCC predominantly to th e proximal tubuli. In the glomeruli of the infarcted areas deposits of TCC were seen as a crescent-like pattern at and immediately beneath t he Bowman's capsule. The expression of cell membrane-associated protec tin was diminished in tubular epithelial cells of the infarction lesio ns. A clue for the possible mechanism of C activation in renal infarct ion was obtained from in vitro experiments, in which the contact of no rmal human serum with urine was observed to lead to the generation of TCC. Thus, in renal ischemic lesions C may become activated when C com ponents enter the intratubular urinary space of ischemic tubuli. Our r esults suggest that local C activation in association with ischemic re nal injury leads to the generation of terminal C complexes and an infl ammatory response whereby a healing process can begin.