Inhibition of neutrophil respiratory burst and degranulation responses to platelet-activating factor by antagonists WEB 2086, CV 6209 and CV 3988.

The effect of three platelet-activating factor (PAF) antagonists, WEB 2086, CV 6209 and CV 3988, on neutrophil respiratory burst activity and degranulation in response to PAF was investigated. Both WEB 2086 and CV 6209 significantly inhibited the respiratory burst and degranulation in response to 400 nM PAF in a dose-dependent manner (10(-8)-10(-5) M). Higher concentrations of CV 3988 were required to inhibit these functions (10(-5) M and above). The three antagonists inhibited both the release of beta-glucuronidase (from azurophilic granules) and vitamin B12 binding protein (from specific granules) in response to PAF. Only a small nonsignificant inhibition of neutrophil function occurred in the absence of PAF. There was no loss of viability after incubation with the three antagonists at the concentrations tested. These antagonists will be useful tools to study the involvement of PAF in neutrophil-mediated tissue damage and inflammation.