The Effect of Hemodialysis and C 5 adesarg # { 176 } n Neutrophil Subpopulations

Alterations in neutrophil subpopulations during human hemodialysis or following injection of C5a,,,, into rabbits were studied. Whereas baseline peripheral blood neutrophils contained approximately 80% of cells that formed rosettes with lgG-sensitized erythrocytes. neutrophils harvested at the granulocyte nadir (20 mm after initiating hemodialysis or the injection of C5a,, ,, arg) were markedly depleted of this population. This was seen in a change in ratio of rosette-forming neutrophils (RFN) to non-rosette-forming neutrophils (non-RFN) from 4:1 at 0 time to 1 :2 at 20 mm. Since non-RFN are less active in assays of adherence and chemotaxis. these alterations in circulating neutrophil populations were reflected in abnormal functional capacity of neutrophils harvested at 20 mm. To study the mechanism of RFN depletion. we investigated the ability of C5a,, , to aggregate various human neutrophil suspensions. Unfractionated neutrophils and RFN demonstrated prompt in vitro aggregation in response to C5a,,,, .rg ‘ whereas this activated complement fragment induced little aggregation in a population enriched for non-RFN. These results may explain the alterations in neutrophil adherence. chemotaxis. phagocytosis. and bactericidal activity. which have been reported to accompany clinical disorders characterized by in vivo complement activation (i.e.. hemodialysis or gram-negative sepsis).