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 [vitronectin, 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 and clusterin, were observed throughout the infarcted areas. The strongest deposits were seen on the membranes of tubular epithelial cells and in the tubular lumina of the infarction areas, especially in the border zone between normal and infarcted tissue. Using markers for different segments of tubuli (Tamm-Horsfall glycoprotein and brush border antigens) it was possible to localize deposits of TCC predominantly to the proximal tubuli. In the glomeruli of the infarcted areas deposits of TCC were seen as a crescent-like pattern at and immediately beneath the Bowman's capsule. The expression of cell membrane-associated protectin was diminished in tubular epithelial cells of the infarction lesions. A clue for the possible mechanism of C activation in renal infarction was obtained from in vitro experiments, in which the contact of normal human serum with urine was observed to lead to the generation of TCC.(ABSTRACT TRUNCATED AT 250 WORDS)
Väkevä
A
A
Department of Bacteriology and Immunology, University of Helsinki, Finland.
Meri
S
S
Lehto
T
T
Laurila
P
P
D003167:Complement Activation; D006801:Humans; D007124:Immunoenzyme Techniques; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007238:Infarction / Q000276:immunology* / Q000473:pathology; D007668:Kidney / Q000098:blood supply* / Q000276:immunology / Q000473:pathology; D008856:Microscopy, Fluorescence; D014556:Urine