CHEMOTAXIS BY HUMAN NEUTROPHILS AND THEIR CYTOKINEPLASTS TREATED WITHINHIBITORS OF NITRIC-OXIDE SYNTHASE - NO SUPPRESSION OF ORIENTATION OR TRAJECTORY

Inhibitors of nitric oxide (NO) synthase are reported to inhibit both the adherence of polymorphonuclear leukocytes (PMN) to substrate and c hemotaxis (directed locomotion) of PMN as determined in Boyden chamber assays, In the current study, we examined both human blood PMN and gr anule-poor motile cytoplasts derived from them (cytokineplasts, CKP), under direct microscopic observation with concomitant time-lapse video recording, for their ability to respond chemotactically to an erythro cyte destroyed by laser microirradiation. In this system we can observ e directly and continuously the orientation and trajectory of PMN befo re, during, and after establishment of a chemotactic gradient, For bot h PMN and CKP we employed three different inhibitors of NO synthase (N -omega-methyl-L-arginine, N-iminoethyl-L-ornithine, and diphenyleneiod onium) in at least twice the concentrations employed to inhibit chemot axis of PMN in Boyden chambers or killing of bacteria in CKP, Although small differences in adhesion might not have been appreciated, treate d PMN and CKP were each indistinguishable from untreated controls in t heir ability to orient in a newly created chemotactic gradient and in their trajectories toward the chemotactic target.