Heparin inhibits the binding of immune complexes to cultured rat mesangial cells.
Glomerular mesangial cells bear Fc receptors which bind immune complexes. Cross-linking of these receptors induces the release of cytokines chemotactic for macrophages; the receptors may also be involved in the localization of large circulating immune complexes to the mesangium. Heparin has been shown to enhance the removal of antigen from the glomeruli of rats with chronic serum sickness glomerulonephritis, and from the isolated perfused rat kidney, so we investigated the effect of heparin on the binding of immune complexes by rat glomerular mesangial cells in culture. Heparin was found almost to eliminate binding of radiolabelled immune complexes to cultured rat mesangial cells. Pretreatment of the cells with heparin for 24 h followed by washing before the addition of immune complexes had the same effect. A parallel study showed that heparin had no effect on immune complex binding to thioglycollate-elicited rat peritoneal macrophages. To investigate the molecular properties required for this effect we treated cultured cells with high- or low-molecular-weight dextran sulphate. High-molecular-weight dextran sulphate was found to inhibit the subsequent binding of immune complexes to the mesangial cells, although the effect appeared to be smaller than with heparin. Low-molecular-weight dextran sulphate had no detectable effect. Subsequent studies showed that heparin is also capable of removing immune complexes which have already bound to mesangial cells in vitro. We conclude that heparin can block the binding of immune complexes to the Fc receptor of cultured mesangial cells, but not to peritoneal macrophages. The success of heparin pretreatment indicates that the effect is on the cells rather than on the complexes in suspension.(ABSTRACT TRUNCATED AT 250 WORDS)
Drakeley
S J
SJ
Department of Pathology, University of Leicester, UK.
Furness
P N
PN
D000818:Animals; D000936:Antigen-Antibody Complex / Q000378:metabolism*; D002478:Cells, Cultured; D016264:Dextran Sulfate / Q000737:chemistry / Q000494:pharmacology; D005920:Glomerular Mesangium / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D006493:Heparin / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008970:Molecular Weight; D051381:Rats; D017208:Rats, Wistar; D011961:Receptors, Fc / Q000187:drug effects / Q000378:metabolism
D000936:Antigen-Antibody Complex; D011961:Receptors, Fc; D006493:Heparin; D016264:Dextran Sulfate