Events that stimulate release of thromboxane B2 in passive heymann nephritis.
The cause of proteinuria in passive Heymann nephritis has been attributed to the activation of the C5b-9 membrane attack complex following the antibody binding on the glomerular epithelial cell. Previous studies have shown an association between release of prostaglandin thromboxane B2 (TxB2) and proteinuria. Whether this release is dependent on antibody binding per se, or on secondary actions subsequent to antibody binding has not been clarified. The present study was designed to address this issue. Antibody binding event was experimentally separated from the proteinuria by employing a rabbit antibody which produces equivalent glomerular binding equal to that produced by a sheep antibody but without causing proteinuria. Comparisons were made with animals injected with the sheep antibody which produces all the hallmarks of the disease, including proteinuria. Animals injected with the rabbit antibody showed glomerular immunofluorescent deposits which were identical to the deposits produced by the control sheep antibody. However, rabbit antibody failed to produce the typical electron-dense subepithelial deposits, complement binding and proteinuria. Comparison of prostaglandin profile in isolated glomeruli revealed that TxB2 was unchanged in rabbit antibody-injected glomeruli (compared with its nonimmune antibody control). On the other hand, glomeruli from sheep antibody-injected animals released 45% higher TxB2 compared with their respective nonimmune antibody control. These data suggest that the binding of antibody per se may not be a sufficient stimulus for TxB2 release. Subsequent events of subepithelial electron dense deposit formation, complement activation, and proteinuria are associated with TxB2 release.
Alavi
N
N
Department of Medicine (Nephrology), Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois 60612, USA.
Singh
A
A
D000818:Animals; D015938:Complement Membrane Attack Complex / Q000378:metabolism; D004195:Disease Models, Animal; D015777:Eicosanoids / Q000378:metabolism; D019085:Fluorescent Antibody Technique, Direct; D005921:Glomerulonephritis / Q000378:metabolism* / Q000473:pathology; D007678:Kidney Glomerulus / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D011507:Proteinuria / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013929:Thromboxane B2 / Q000378:metabolism*
D015938:Complement Membrane Attack Complex; D015777:Eicosanoids; D013929:Thromboxane B2