Interaction of platelet-activating factor with cultured guinea pig tracheal epithelial cells.
The present study has examined the interaction of platelet-activating factor (PAF) with cultured guinea pig tracheal epithelial cells (GTE). PAF stimulated GTE to release endogenous arachidonic acid and metabolize it to prostaglandins E2 and F2 alpha (PGE2 and PGF2 alpha). Prostanoid production by GTE in response to PAF was dose-dependent (0.1-100 nM) and was maximal within 5 min. PGE2 and PGF2 alpha levels increased by 3.3 +/- 0.8 and 3.2 +/- 0.6 ng/10(6) cells respectively over basal levels in response to 100 nM-PAF. The ability of GTE to synthesize and/or catabolize PAF was also examined. GTE readily incorporated [3H]acetate into a product which migrated on t.l.c. with PAF. However, further characterization of this product suggested that label had not been incorporated into PAF, but rather that it was incorporated into another lipid product with chromatographic characteristics similar to those of PAF. In contrast, GTE readily metabolized PAF to inactive products. When [3H]PAF was incubated with GTE, 50% of the total [3H]PAF added was catabolized in approx. 15 min. The major route of catabolism of PAF by GTE was the deacetylation-reacylation pathway, which yielded 1-O-[3H]alkyl-2-acyl-sn-glycerophosphocholine. Determination of the nature of the long-chain acyl group incorporated into the sn-2 position of the newly synthesized products revealed that oleic and linoleic acids were the major fatty acids present. Taken together, these results suggest that respiratory epithelial cells respond to stimulation by PAF with enhanced production of PGE2 and PGF2 alpha, and also have the capacity to modulate inflammatory reactions in the airways by their ability to degrade this potent inflammatory mediator.
Churchill
L
L
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21224.
Chilton
F H
FH
Proud
D
D
D000818:Animals; D002478:Cells, Cultured; D015237:Dinoprost / Q000096:biosynthesis; D004848:Epithelium / Q000378:metabolism / Q000502:physiology; D006168:Guinea Pigs; D008297:Male; D010972:Platelet Activating Factor / Q000031:analogs & derivatives / Q000096:biosynthesis / Q000378:metabolism*; D014132:Trachea / Q000378:metabolism*
D010972:Platelet Activating Factor; D015237:Dinoprost