The Journal of Immunology, Vol 144, Issue 9 3513-3517, Copyright © 1990 by American Association of Immunologists

ARTICLES

Selective activation of human monocytes by the platelet-activating factor analog 1-O-hexadecyl-2-O-methyl-sn-glycero-3-phosphorylcholine

JK Rose, RA Debs, R Philip, NM Ruis and FH Valone
Department of Medicine, VA Medical Center, San Francisco, CA 94121.

The capacity of platelet-activating factor (PAF) and its 2-O-methyl analog (methoxy-PAF) to activate human monocytes, neutrophils and platelets were compared. Both PAF and methoxy-PAF increased monocyte cytotoxicity toward WEHI 164 cells with a maximal increase in cell killing at 100 pM to 1 nM. Methoxy-PAF was slightly, but significantly, more potent than PAF for increasing cytotoxicity. PAF and methoxy-PAF increased monocyte release of TNF two- to three-fold above control release with no difference in their potency. Methoxy-PAF increased cell- associated TNF maximally after 2 to 3 h of incubation and increased TNF release maximally after 5 to 18 h of incubation. PAF induced release of the neutrophil granule enzyme beta-glucuronidase with maximal net release of 15 to 20% at 100 nM PAF whereas methoxy-PAF did not induce release of beta-glucuronidase. Similarly, 10 nM PAF induced 30% platelet aggregation whereas methoxy-PAF induced aggregation only at 1000-fold higher concentrations. Analysis of PAF and methoxy-PAF metabolism by monocyte and serum acylhydrolases indicates that methoxy- PAF is substantially more resistant than PAF to degradation by these enzymes. These observations indicate that methoxy-PAF activates monocytes selectively and suggest that this phospholipid or a related compound could be used for in vivo immunotherapy.