Mechanisms of clearance of immune complexes from peritubular capillaries in the rat.
These experiments evaluated extraglomerular sites of renal immune complex (IC) deposition and specific features of host capability to remove these IC. Ex vivo perfusion of rat kidneys with the endothelium binding lectin concanavalin A (con A) followed by rabbit anti con A IgG results in a subendothelial IC nephritis in glomerular capillaries (GC) and diffuse IC formation with complement (C3) deposition in peritubular capillaries (PC). Histologic, immunofluorescence, and ultrastructural studies were performed at 10 minutes and 1, 4, and 24 hours after perfusion. At 10 minutes, strong linear binding of con A, rabbit IgG, and rat C3 to the endothelium was detected by immunofluorescence in both GC and PC. In GC this was followed by endothelial cell swelling and denudation (1 hour) with platelet and neutrophil infiltration and formation of subendothelial IC deposits which persisted at 4 and 24 hours. In contrast, some PC endothelial swelling was also present at 10 minutes and 1 hour, but ICs (IgG, con A, C3) were capped and shed into capillary lumina at 1 to 2 hours with complete clearance of IC by 4 hours. Selective neutrophil depletion, by antisera and irradiation, and complement depletion with cobra venom factor, delayed clearance of PC IC by several hours but complete clearance of IC with restored structural integrity of PC was still achieved by 24 hours. Platelet depletion had no effect on PC IC clearance. These studies demonstrate a model for study of PC IC. Such a model may aid our understanding of lupus nephritis in which extensive GC IC deposits associated with severe inflammatory injury may coexist with PC deposits. Efficient clearance of IC in PC compared with GC may be due to differences in hemodynamic forces, amounts of IC formed in each of these sites, differences in binding of IC to subendothelial basement membrane, or phenotypic specialization of the endothelium lining these two different capillary beds.
Alpers
C E
CE
Department of Pathology, School of Medicine, University of Washington, Seattle 98195.
Hudkins
K L
KL
Pritzl
P
P
Johnson
R J
RJ
D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000502:physiology; D000936:Antigen-Antibody Complex / Q000378:metabolism*; D001792:Blood Platelets / Q000502:physiology; D002196:Capillaries / Q000378:metabolism*; D003208:Concanavalin A / Q000276:immunology / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism; D005293:Ferritins / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D007684:Kidney Tubules / Q000098:blood supply* / Q000276:immunology / Q000378:metabolism; D007962:Leukocytes / Q000502:physiology; D008297:Male; D009393:Nephritis / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D011919:Rats, Inbred Strains
D000906:Antibodies; D000936:Antigen-Antibody Complex; D007074:Immunoglobulin G; D003208:Concanavalin A; D005293:Ferritins