5-LIPOXYGENASE EXPRESSION IN LANGERHANS CELLS OF NORMAL HUMAN EPIDERMIS

We studied expression of the 5-lipoxygenase (5-LO) pathway in normal h uman skin, In situ hybridization revealed a 5-LO mRNA-containing epide rmal cell (EC) population that was predominantly located in the midpor tion of the spinous layer, in outer hair root sheaths, and in the epit helial compartment of sebaceous glands. Examination of skin specimens by immunohistochemistry and of primary ECs by flow cytometry mapped th e 5-LO protein exclusively to Langerhans cells (LCs), The LC 5-LO prot ein was largely found in the nuclear matrix, in nuclear envelopes, and perinuclear regions as indicated by in situ confocal laser scan micro scopy, Reverse transcription-PCR and immunoblot analyses of purified p rimary EC populations further indicated that LCs are major 5-LO expres sing cells, Enriched primary LCs were also found to contain 5-LO activ ating protein (FLAP), leukotriene (LT) C-4 synthase, and LTA(4) hydrol ase, By contrast, 5-LO, FLAP, and LTC4 synthase were undetectable or l argely reduced, but LTA(4) hydrolase transcripts and protein were iden tified in ECs depleted of LCs, These data show that naive LCs are majo r, and possibly the sole, 5-LO pathway expressing cells in the normal human epidermis.