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

• Published in: Journal of leukocyte biology 1996-02, Vol.59 (2), p.219-228
• Main Authors: Pinckard, R. Neal, Prihoda, Thomas J.
• Format: Article
• Language: English
• Subjects: acyl‐PAF; Adrenergic beta-Antagonists - pharmacology; alkyl‐PAF; Amino Acid Sequence; Anions; Azepines - pharmacology; Complement C5a - pharmacology; Drug Synergism; Female; Humans; Male; Molecular Sequence Data; N-Formylmethionine Leucyl-Phenylalanine - pharmacology; Neutrophil Activation - drug effects; Neutrophils - drug effects; Neutrophils - metabolism; PAF receptors; Phosphatidylcholines - pharmacology; Platelet Activating Factor - analogs & derivatives; Platelet Activating Factor - pharmacology; Platelet Aggregation Inhibitors - pharmacology; PMN priming; Recombinant Proteins - pharmacology; superoxide anion; Superoxides - metabolism; Triazoles - pharmacology; WEB 2086
• ISSN: 0741-5400; 1938-3673
• DOI: 10.1002/jlb.59.2.219

Alkyl‐PAF induced two components of polymorphonuclear leukocyte (PMN) pruning 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 pruning 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 pre‐treated 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 printing. PMN pruning by acyl‐PAF (1 nM–1 μM) had characteristics identical to those of alkyi‐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.