Beta2 integrins are required for neutrophil degranulation induced by hemodialysis membranes.

An untoward consequence of hemodialysis is degranulation of peripheral blood neutrophils. The mechanisms that mediate this process, however, have not been conclusively identified. In the present study, the participation of complement activation and beta 2 integrins (CD11/CD18) in hemodialysis-induced neutrophil degranulation was investigated. Incubation of neutrophils with cuprophan membrane stimulated the release of very small amounts of the cytoplasmic granular protein, elastase. This release was markedly enhanced by the addition of plasma. Inactivation of complement reduced degranulation by approximately 60%, but the contribution of anaphylatoxins C3a and C5a to the degranulation process was modest. Treatment of plasma with EDTA completely abolished neutrophil degranulation in the presence of cuprophan membrane. Further, when incubated with plasma and cuprophan membrane, neutrophils that are deficient in beta 2 integrins released only 10% as much elastase as normal cells. Together, these observations strongly suggest that one or more members of the beta 2 integrin family of receptors is essential for cuprophan membrane-induced neutrophil degranulation and that both complement-related and noncomplement-related factors serve as receptor ligands.