Complement activation and pulmonary leukostasis during nylon fiber filtration leukapheresis

Filtration leukapheresis (NFFL) is similar to hemodialysis in that donor blood is pumped over a foreign polymeric surface and a profound neutropenia occurs early during the procedure. Suspecting complement (C)-mediated leukostasis, the authors studied nine leukaphereses of normal donors as well as plasma incubated with nylon in vitro. Granulocyte (PMN)-aggregating activity, identified in earlier studies with C5a, was found both in nylon-incubated plasma and in plasma from the NFFL return line. EDTA, EGTA, heat, and hydrazine-inhibition studies suggested alternative pathway C dependence, confirmed by the demonstration of C3 and factor B conversion. Gel filtration, ultrafiltration, and antiserum-inhibition studies identified C5a as the aggregating agent. Neutropenia during NFFL was more profound than could be explained on the basis of filter trapping of PMN; sequestration was inferred. A mild but steady decrement was noted in pulmonary CO diffusion during NFFL, and two of four donors tested showed elevations in closing volumes. These observations were nonspecific but consistent with the suggestion that as in hemodialysis such sequestration may occur in the lungs. NFFL-harvested PMN were poorly responsive in vitro to C-activated plasmas as chemoattractants or aggregating agents. The chemotactic defect was mimicked by deliberate preexposure of PMN to activated C. This functional impairment of NFFL granulocytes suggests that modulation of C activation during NFFL may improve the usefulness of the technique.