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Soluble complement receptor type 1 inhibits complement activation induced by hemodialysis membranes in vitro

1994; Elsevier BV; Volume: 46; Issue: 6 Linguagem: Inglês

10.1038/ki.1994.468

1523-1755

Alfred K. Cheung, Charles Parker, Mary Hohnholt,

Dialysis and Renal Disease Management

A variety of bioincompatible events that occur during hemodialysis have been attributed to complement activation. However, cause-effect relationships have been based primarily on indirect evidence and the results of in vitro studies, because an acceptable method for inhibiting complement activation during clinical hemodialysis has been unavailable. Methods for inactivating complement in vitro are available, but the most commonly used of these techniques (heat inactivation and chelation of divalent cations) lack specificity. A recombinant, soluble form of human complement receptor type 1 (sCR1) has been developed recently and shown to inhibit complement activation in vivo. Here, we report studies aimed at determining the effects of sCR1 on dialysis-induced complement activation and neutrophil degranulation. In a concentration dependent fashion, sCR1 inhibited plasma complement activation by cuprophan membrane in vitro. Using a maximally inhibitory concentration (30 micrograms/ml), sCR1 blocked generation of C3a(desArg) by cuprophan, cellulose acetate, and polymethylmethacrylate membranes by 90%, 84%, and 84%, respectively. In contrast, elastase release (a measure of neutrophil degranulation) was inhibited by 70%, 70%, and 44%, respectively, suggesting that dialysis-induced neutrophil activation is mediated in part by noncomplement dependent mechanisms. Both heat- and EDTA-treatment of plasma abolished dialysis membrane-induced complement activation, but these treatments also affected noncomplement dependent components of the degranulation process. These observations show that, compared with other commonly used methods for inhibiting dialysis induced complement activation, sCR1 is more specific. An additional advantage of sCR1 is its potential for use in the clinical setting.