Clinical Investigation

Kidney International (1991) 40, 1123–1133; doi:10.1038/ki.1991.324

Adherence of neutrophils to hemodialysis membranes: Role of complement receptors

Alfred K Cheung1, Mary Hohnholt1 and Janice Gilson1

1Renal Section and Research Service, Veterans Affairs Medical Center, and Division of Nephrology, University of Utah School of Medicine, Salt Lake City, Utah, USA

Correspondence: Alfred K Cheung MD, Renal Section (11H), Veterans Affairs Medical Center, 500 Foothill Blvd., Salt Lake City, Utah 84148, USA.

Received 2 April 1991; Revised 30 July 1991; Accepted 30 July 1991.

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Abstract

Adherence of neutrophils to hemodialysis membranes: Role of complement receptors. Complement activation occurs during hemodialysis using cellulosic dialysis membranes with the consequent deposition of C3 activation and degradation products on the membrane surface. To determine if these complement fragments are functionally active, we examined their capacity to mediate leukocyte adherence to cuprophan membranes. Immunoblotting of proteins eluted from plasma-treated cuprophan membranes confirmed the presence of both C3b and iC3b. Incubation of cuprophan membranes with heparinized whole blood resulted in adherence of leukocytes but not erythrocytes. Neutrophils were the primary cell type bound, with monocytes comprising less than 5% of the adherent cells. Studies using indium-labeled neutrophils demonstrated that the binding was plasma dependent and increased with time up to two hours. Neutrophil binding was inhibited by preincubation of the plasma-treated cuprophan membrane with anti-C3 or preincubation of neutrophils with an antibody directed against the alpha chain of complement receptor type 3 (CR3). These observations indicate that iC3b deposited on cuprophan membrane surface as a result of complement activation mediates neutrophil adherence via interaction with CR3. They also support the hypothesis that, in addition to the anaphylatoxins released into the fluid phase, complement activation products that remained membrane bound during hemodialysis also stimulate pathophysiological responses.

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