Heparin decreases mesangial matrix accumulation after selective antibody-induced mesangial cell injury.
Anti-rat thymocyte antibody-induced injury of glomerular mesangial cells is characterized initially by lysis (1 h) and is followed by proliferation (beginning at 3 to 4 days), with resolution that can include a focal increase in mesangial matrix (by 28 days). Chronic administration (every 12 h) of heparin (anticoagulant or nonanticoagulant) resulted in a decrease in antibody-induced mesangial cell proliferation, which, in turn, was associated with a decrease in the size and number of areas of focal mesangial matrix increase. The effect could not be attributed to the effect of heparin on complement, to alterations in the small numbers of la-positive cells that characterize the lesion, or to binding of antibody to glomeruli. The beneficial effects of heparin in reducing mesangial cell proliferation, with a subsequent reduction in matrix increase, suggest that mesangial cell responses are a major element in the development of at least some forms of glomerulosclerosis. The possible mechanisms by which these effects of heparin may be achieved are discussed.
Tang
W W
WW
Department of Immunology, Scripps Research Institute, La Jolla, CA 92037.
Wilson
C B
CB
D000818:Animals; D000961:Antilymphocyte Serum / Q000276:immunology / Q000633:toxicity*; D002455:Cell Division / Q000187:drug effects; D003165:Complement System Proteins / Q000032:analysis; D005109:Extracellular Matrix / Q000378:metabolism*; D005260:Female; D005455:Fluorescent Antibody Technique; D005920:Glomerular Mesangium / Q000187:drug effects* / Q000503:physiopathology / Q000648:ultrastructure; D006493:Heparin / Q000494:pharmacology*; D010314:Partial Thromboplastin Time; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000276:immunology*
D000961:Antilymphocyte Serum; D006493:Heparin; D003165:Complement System Proteins