Distribution of monohydroxy fatty acids in specific human epidermal phospholipids

Monohydroxy derivatives of polyunsaturated fatty acids such as arachidonic acid (AA) and linoleic acid (LA) can modulate inflammation and epidermal proliferation. The purpose of this study was to determine the in vivo distribution of the AA derivatives; 12- and 15-hydroxyeicosatetraenoic acid (12-HETE and 15-HETE) and the LA derivatives; 9- and 13-hydroxyotadecadienoic acid (9-HODE and 13-HODE) in specific phospholipids of normal human skin. Lipids were extracted from 6 normal keratome skin biopsies and phospholipids were separated into the major classes by two-dimensional thin layer chromatography. Monohydroxy fatty acids (MHFAs) released from specific phospholipids after treatment with phospholipase A2 were identified by reversed phase and straight phase high-performance liquid chromatography and UV-absorption spectra. Unesterified MHFAs were determined in a similar way. 9-HODE, 13-HODE and 15-HETE were detectable in phosphatidylcholine (PC), phosphatidylinositol (PI) and phosphatidylethanolamine (PE). Interestingly, 12-HETE was not detectable in these phospholipids, although the unesterified 12-HETE was detectable in amounts similar to unesterified 15-HETE. Esterified 15-HETE was equally distributed between PI and PC, in which 15-HETE was predominant, accounting for 60% and 69% of the total MHFAs, respectively (p < 0.05). These results demonstrate that the LA derivatives 9-HODE and 13-HODE, as well as the AA derivative 15-HETE, are esterified to PC, PI and PE of normal human epidermis in vivo. The possibility remains that 9-HODE, 13-HODE and 15-HETE, may mediate their biological effects by being incorporated into specific phospholipids.