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Modulation of neutrophil oxidative responses to soluble stimuli by
platelet-activating factor
JC Gay, JK Beckman, KA Zaboy and JN Lukens
The role of platelet activating factor (PAF) as a regulator of human
neutrophil superoxide (O2-) generation in response to soluble and
particulate stimuli was examined. At concentrations greater than 10(-7)
mol/L, PAF alone induced a brief burst of O2- production. When cells were
exposed to PAF and either the chemotactic peptide n-formyl-
methionyl-leucyl-phenylalanine (FMLP 10(-7) mol/L) or the tumor promoter
phorbol myristate acetate (PMA 10 ng/mL), a marked synergistic augmentation
of O2- release was noted when compared to control cells stimulated with
FMLP or PMA alone. Mean percentage of enhancement by 10(-5) mol/L of PAF
was 297% +/- 35% (n = 9) of control responses to FMLP and 185% +/- 16% (n =
3) of control responses to PMA. Consistent enhancement occurred with PAF
concentrations of as low as 10(-9) mol/L. Enhancement could be demonstrated
when neutrophils were exposed to PAF either at the same time as, or up to
60 minutes prior to, the second stimulus, and was neither reversed by
removal of PAF from the medium prior to addition of FMLP or PMA nor
dependent on the presence of extracellular divalent cations. Continuous
recordings revealed that the enhancement was due to an increased maximal
rate of O2- production. In contrast, PAF concentrations up to 10(-5) mol/L
had only a minimal effect on the response to neutrophils to opsonized
zymosan. Analysis of the enhancing properties of lipids structurally
related to PAF revealed that the critical moiety was the saturated fatty
acid at position 1. These results indicate the presence of a PAF-mediated
positive feedback loop whereby the oxidative burst induced by some soluble
stimuli is augmented. Modulation of neutrophil O2- production by PAF may
serve to amplify neutrophil oxidative responses at sites of inflammation.
Volume 67,
Issue 4,
pp. 931-936,
04/01/1986
Copyright © 1986 by The American Society of Hematology
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