Stimulus-specific neutrophil aggregation: evaluation of possible mechanisms for the stimulus-response apparatus

We have assessed the effects of formyl peptides, leukotrienes, zymosan-activated serum (ZAS), and calcium ionophore A 23187 on the aggregation response of human neutrophils to characterize the mechanisms involved, particularly the possible contribution of the concomitant burst of oxidative metabolism and degranulation. We found that the tested stimuli induced aggregation waves highly characteristic for each agent. With formyl peptides, such as f-Met-Leu-Phe (fMLP), f-Met-Met-Met-Met (fMMMM), and f-Nle-Leu-Phe-Nle-Tyr-Leu (fNLPNTL), peaks appeared after greater than 60 seconds and were followed by a slow disaggregation. In contrast, leukotriene B4 (LTB4) and its omega-oxidized metabolites, 20-OH-LTB4 and 20-COOH-LTB4, induced rapidly occurring peaks that were maximal after 15 to 30 seconds and that were followed by a rapid and marked disaggregation. ZAS induced peak values after 30 to 90 seconds, and disaggregation kinetics were between fMLP and LTB4. A 23187 in high concentrations (10 to 50 mumol/L) elicited biphasic aggregation waves, whereas lower concentrations induced less pronounced and continuous aggregation responses. Superoxide dismutase, catalase, mannitol, and Tiron did not influence any of the aggregation characteristics. Colchicine and indomethacin did have some effects on peak values but not on the characteristic curve profiles, whereas cytochalasin B had a profound effect on the aggregation response for all tested stimuli. Neutrophils from a patient with chronic granulomatous disease exhibited aggregation responses similar to those of controls.(ABSTRACT TRUNCATED AT 250 WORDS)