The dynamics of the response of normal skin to single and multiple epicutaneous leukotriene B4 applications analysed by three-colour flow cytometry
Glade CP, Botermans RJ, van Erp PE, van de Kerkhof PC
Leukotriene B4 (LTB4) is a potent chemoattractant and a well-established stimulator of DNA-synthesis in keratinocytes. Previously, repeated applications of LTB4 have been reported to induce a topically defined tachyphylaxis with respect to the extravasation of polymorphonuclear neutrophils. The aim of the present study was to quantify epidermal proliferation (% basal keratinocytes in S- and G2M phase), epidermal keratinization (% keratin 10-positive keratinocytes) and the appearance 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 LTB4. Using three-colour flow cytometry, we could reconfirm that the response to one single epicutaneous application of LTB4 was characterized by a marked increase of the percentage of basal keratinocytes in S- and G2M phase, and a marked increase of non-keratinocytes. Repeated applications of LTB4 induced a moderate increase of the percentage of cells in S- and G2M phase and a moderate increase of the percentage of keratin 10-positive keratinocytes. Remarkably, the percentage of non-keratinocytes had decreased following repeated applications of LTB4, compared to unchallenged normal skin. The present study suggests that chronic exposure of normal skin to LTB4 induces changes which differ markedly from the histological features of the chronic psoriatic lesion. Therefore, LTB4 is unlikely to be responsible for the perpetuation of the psoriatic plaque.