Alkyl-PAF and acyl-PAF human neutrophil priming for enhanced fMLP- and rC5a-induced superoxide anion production

Abstract

Alkyl-PAF induced two components of polymorphonuclear leukocyte (PMN) priming for enhanced fMLP- and rC5a-induced superoxide anion (O2-) production. Component A priming had a shallow, linear alkyl-PAF concentration-response slope (10 pM-1 nM), and component B priming had a significantly steeper concentration-response slope (1-100 nM alkyl-PAF). Whereas the extent of component B priming decayed significantly within 5-10 min after pretreatment of PMNs with alkyl-PAF, component A priming was completely stable. WEB 2086, a specific and potent PAF receptor antagonist, abolished component A priming when PMNs were simultaneously stimulated with alkyl-PAF and either fMLP or rC5a but only partially reduced component B priming. However, whereas WEB 2086 also obliterated component A priming when PMNs were pretreated with alkyl-PAF for 2.5, 5, or 10 min prior to fMLP stimulation, WEB 2086 had little or no inhibitory effect on component B priming. Paradoxically, WEB 2086 significantly augmented alkyl-PAF-induced component B priming for enhanced rC5a-induced PMN O2. production yet concomitantly obliterated component A priming. PMN priming by acyl-PAF (1 nm-1 micron) had characteristics identical to those of alkyl-PAF-induced component A priming. These studies suggest that there are at least two effector pathways modulating alkyl-PAF-induced PMN respiratory burst priming. They are also consistent with the notion that component A priming is initiated via high-affinity PAF receptors and component B priming is mediated through low-affinity PAF receptors; and whereas alkyl-PAF interacts with both high- and low-affinity PAF receptors, both acyl-PAF and WEB 2086 preferentially bind to the high-affinity PAF receptors.

Expression of the Platelet-activating Factor Receptor Results in Enhanced Ultraviolet B Radiation-induced Apoptosis in a Human Epidermal Cell Line

“…This priming effect of the PAF-R on apoptosis resembles PAF effects on PMN superoxide production. PAF alone does not induce detectable superoxide production in PMNs unless they are pretreated with cytochalasin B or propranolol; yet pretreatment with PAF can augment PMN superoxide production in response to fMLP or C5A (44).…”