Acute keratinocyte damage stimulates platelet-activating factor production

Recent evidence suggests that the phosphocholine-derived lipid mediator pla telet-activating factor (PAF) is involved in keratinocyte function and cuta neous inflammation. PAF is found in various inflammatory skin diseases, and intradermal injection of PAF directly results in cutaneous inflammation. K eratinocytes also synthesize PAF and related 1-acyl species in response to ionophores, cytokines and growth factors, and in response to activation of the epidermal PAF receptor. Since keratinocytes are routinely exposed to po tential damage by thermal or oxidative stressors with resultant induction o f cutaneous inflammation, the objective of these studies was to assess whet her exogenous thermal or oxidative damage can induce the production of PAF and related 1-acyl species, Cells of the immortalized human keratinocyte ce ll line HaCaT were subjected to acute heat or cold, or treatment with the p ro-oxidant lipid tertiary butyl hydroperoxide, and PAF and 1-palmitoyl-2-ac etyl-GPC were measured by gas chromatography/mass spectrometry, We report t hat these diverse toxic stimuli resulted in the accumulation of these biolo gically active lipids. These studies suggest that the PAF system is involve d in the inflammatory response seen following acute epidermal damage.