Differential activation of human skin cells by platelet activating factor: stimulation of phosphoinositide turnover and arachidonic acid mobilization in keratinocytes but not in fibroblasts.
Treatment of cultured adult human keratinocytes with platelet activating factor (PAF) resulted in a rapid, dose dependent accumulation of inositol phosphates. Inositol trisphosphate (IP3), inositol bisphosphate (IP2) and inositol phosphate (IP) were elevated within 15 seconds of exposure to PAF (1 microM). Lyso-PAF, phosphatidylcholine (PC) and lyso-PC had no effect on levels of inositol phosphates, indicating that the effect of PAF was specific. PAF also raised cellular 1,2-diacylglycerol content (2-fold) within two minutes of addition and stimulated mobilization of arachidonic acid (AA) and release of prostaglandin E2. In contrast, PAF did not stimulate phosphoinositide turnover or AA release in cultured dermal fibroblasts. These results suggest that the inflammatory effects of PAF in human skin result, at least in part, from its ability to directly activate keratinocytes and stimulate release of pro-inflammatory eicosanoids.
Fisher
G J
GJ
Department of Dermatology, University of Michigan Medical Center, Ann Arbor 48109.
Talwar
H S
HS
Ryder
N S
NS
Voorhees
J J
JJ
D000328:Adult; D001095:Arachidonic Acids / Q000378:metabolism*; D002478:Cells, Cultured; D015232:Dinoprostone / Q000096:biosynthesis; D004817:Epidermis / Q000187:drug effects / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007294:Inositol / Q000378:metabolism; D007295:Inositol Phosphates / Q000096:biosynthesis; D007633:Keratins / Q000378:metabolism; D007700:Kinetics; D010716:Phosphatidylinositols / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000494:pharmacology*; D012867:Skin / Q000187:drug effects / Q000378:metabolism*
D001095:Arachidonic Acids; D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D010972:Platelet Activating Factor; D007294:Inositol; D007633:Keratins; D015232:Dinoprostone