NEUTROPHIL REACTIVE OXYGEN SPECIES PRODUCTION DURING HEMODIALYSIS - ROLE OF ACTIVATED PLATELET-ADHESION TO NEUTROPHILS THROUGH P-SELECTIN

Platelet interaction with leukocytes can occur to a significant degree during hemodialysis, but it remains to be determined what pathophysio logical consequences stem from the intradialytic formation of platelet -leukocyte coaggregates. By the use of flow cytometry techniques, this study was set out to analyze intradialytic platelet-neutrophil coaggr egate formation and neutrophil hydrogen peroxide production from 10 en d-stage renal disease patients each dialyzed with cuprophane and polya crylonitrile membranes, Platelet-neutrophil coaggregates increased dur ing dialysis with cuprophane, whereas no changes occurred with polyacr ylonitrile membranes, Dialysis with cuprophane, unlike that with polya crylonitrile, also resulted in a significant increase in neutrophil hy drogen peroxide production 10 mill after dialysis initiation which per sisted at significantly higher levels than predialysis values through the first 20 min. We found that the increased hydrogen peroxide produc tion by neutrophils essentially occurred in concomitance with neutroph il-platelet coaggregation, Intracellular fluorescence representing hyd rogen peroxide formation significantly increased through the first 20 min of cuprophane dialysis in neutrophils aggregated to platelets, By contrast, no change occurred in neutrophils not aggregated to platelet s, Neutrophils which had formed aggregates with platelets produced hig her hydrogen peroxide levels, as assessed by significantly higher fluo rescence values, than non-aggregate-forming neutrophils at all time po ints tested, The phenomenon was duplicated in vitro when ADP-activated normal platelets were incubated with neutrophil cells but was largely inhibited when ADP-activated platelets were treated with anti-P-selec tin antibody before incubation with neutrophils. These results strongl y suggest that platelet-neutrophil aggregates occurring during hemodia lysis, representing cell-cell interactions with pathophysiological eff ects, may serve as a new parameter to assess biocompatibility.