Enhanced human monocyte cytotoxicity by platelet-activating factor.
The capacity of platelet-activating factor (PAF) to enhance human monocyte cytotoxicity for WEHI 164 cells was examined. Spontaneous monocyte cytotoxicity was 24 +/- 2% (mean +/- SEM, n = 9). Preincubation of monocytes with 1 pM-1 nM PAF for 18 hr significantly enhanced cytotoxicity in a dose-related manner, whereas less enhancement was observed at PAF concentrations above 1 nM. Maximal PAF-induced cytotoxicity was 68 +/- 6%, which was similar to that induced by optimal concentrations of tumour necrosis factor (TNF) and interferon-gamma. The specific PAF antagonist kadsurenone inhibited PAF-induced cytotoxicity but not TNF-induced cytotoxicity. The inactive PAF analogues lysoPAF and enantioPAF did not increase monocyte cytotoxicity. Two observations suggest that TNF mediates PAF-induced cytotoxicity: specific anti-TNF antibodies inhibited PAF-induced cytotoxicity toward WEHI 164 cells, and PAF did not enhance cytotoxicity to TNF-resistant cells. PAF represents a distinct class of phospholipid monocyte activators that increase monocyte cytotoxicity by TNF-dependent mechanisms.
Valone
F H
FH
Department of Medicine, VA Medical Center, San Francisco, CA 94143.
Philip
R
R
Debs
R J
RJ
D001572:Benzofurans / Q000494:pharmacology; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D007536:Isomerism; D017705:Lignans; D009000:Monocytes / Q000276:immunology*; D010972:Platelet Activating Factor / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D001572:Benzofurans; D017705:Lignans; C029271:O-deacetyl platelet activating factor; D010972:Platelet Activating Factor; D014409:Tumor Necrosis Factor-alpha; C044540:kadsurenone