BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS Pages 1344-1350 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 (IP ), seconds o ! inositol bisphosphate (IP,) and inositol phosphate (IP) were elevated within 15 exposure to PAF (1pM). Lyso-PAF, phosphatidylcholine (PC) and lyso-PC had no effeet on levels of inositol phosphates, indicating that the effect of PAF was specific. PAF also raised cellular 1,2-diacylglycerol content (a-fold) within two minutes of addition and stimulated mobilization of arachidonic acid (AA) and release of prostaglandin Es. 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 stimutate release of pro-inflammatory eicosanoids.