THE DYNAMICS OF THE RESPONSE OF NORMAL SKIN TO SINGLE AND MULTIPLE EPICUTANEOUS LEUKOTRIENE B-4 APPLICATIONS ANALYZED BY 3-COLOR FLOW-CYTOMETRY

Leukotriene B-4 (LTB(4)) is a potent chemoattractant and a well-establ ished stimulator of DNA-synthesis in keratinocytes. Previously, repeat ed applications of LTB(4) have been reported to induce a topically def ined tachyphylaxis with respect to the extravasation of polymorphonucl ear neutrophils. The aim of the present study was to quantify epiderma l proliferation (% basal keratinocytes in S- and G(2)M phase), epiderm al keratinization (% keratin 10-positive keratinocytes) and the appear ance of ''non-keratinocytes'' including melanocytes, Langerhans' cells and infiltrate cells (% vimentin-positive cells) in order to further elucidate the effect of chronic exposition of normal skin to LTB(4). U sing three-colour flow cytometry, we could reconfirm that the response to one single epicutaneous application of LTB(4) was characterized by a marked increase of the percentage of basal keratinocytes in S- and G(2)M phase, and a marked increase of non-keratinocytes. Repeated appl ications of LTB(4) induced a moderate increase of the percentage of ce lls in S- and G(2)M phase and a moderate increase of the percentage of keratin 10-positive keratinocytes. Remarkably, the percentage of nonk eratinocytes had decreased following repeated applications of LTB(4), compared to unchallenged normal skin, The present study suggests that chronic exposure of normal skin to LTB(4) induces changes which differ markedly from the histological features of the chronic psoriatic lesi on, Therefore, LTB(4) is unlikely to be responsible for the perpetuati on of the psoriatic plaque.