Alkyl-PAF and acyl-PAF human neutrophil priming for enhanced fMLP- and rC5a-induced superoxide anion production.
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.
Pinckard
R N
RN
Department of Pathology, The University of Texas Health Science Center, San Antonio 78284-7750, USA.
Prihoda
T J
TJ
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000595:Amino Acid Sequence; D000838:Anions; D001381:Azepines / Q000494:pharmacology; D015936:Complement C5a / Q000494:pharmacology*; D004357:Drug Synergism; D005260:Female; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D018375:Neutrophil Activation / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000494:pharmacology*; D010972:Platelet Activating Factor / Q000031:analogs & derivatives* / Q000494:pharmacology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism*; D014230:Triazoles / Q000494:pharmacology
C098944:1-hexadecanoyl-2-acetylphosphatidylcholine; D000319:Adrenergic beta-Antagonists; D000838:Anions; D001381:Azepines; D010713:Phosphatidylcholines; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D011994:Recombinant Proteins; D014230:Triazoles; C052518:WEB 2086; D013481:Superoxides; C037145:1-hexadecyl-2-acetyl-glycero-3-phosphocholine; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015936:Complement C5a