THE PARTICIPATION OF PROLIFERATIVE KERATINOCYTES IN THE PREIMMUNE RESPONSE TO SENSITIZING AGENTS

The aims of this study were to investigate whether keratinocytes are c apable of playing a direct preimmune role in the pathophysiology of al lergic contact dermatitis (ACD) and to examine to what extent the degr ee of differentiation might influence this, We measured the ability of sensitizing agents to up-regulate intercellular adhesion molecule 1 ( ICAM-1) expression in cultured normal human keratinocytes (NHK) and in the transformed human keratinocyte HaCaT cell line, In proliferative HaCaT cells, following a 24h exposure, nickel compounds, para-phenylen ediamine (pPD) and 1-chloro-2,4-dinitrobenzene produced a concentratio n-dependent up-regulation of ICAM-1 expression without reducing cell v iability, while K2Cr2O7 led to ICAM-1 up-regulation at cytotoxic conce ntrations, and CrCl3 was without effect, In NHK, NiSO4 and pPD induced ICAM-1 expression to a significantly greater extent in proliferative cells than in differentiated cells, where involucrin expression was me asured to assess the differentiation state. NiSO4- or pPD-pretreatment of proliferative HaCaT cells enhanced T-cell binding, which was aboli shed by neutralizing antibodies to ICAM-1 or CD18, Our investigations concerning the involvement of oxidative stress in the induction of ICA M-1 expression in response to sensitizing agents were inconclusive, Th e oxidizing agents FeCl3 and H2O2 up-repulated ICAM-1 expression in Ha CaT cells but there was no clear relationship between the ability of a gents to induce ICAM-1 expression and their ability to alter the level s of reduced glutathione. Although pPD increased interleukin-1 alpha r elease from NHK, this cytokine was not capable of inducing ICAM-1 expr ession in NHK. Tumour necrosis factor-alpha, which does induce ICAM-1 expression in NHK, was not detected in response to pPD, arguing agains t an autocrine pathway of ICAM-1 induction in response to pPD. In summ ary, we report the direct interaction of sensitizing agents with kerat inocytes leading to the generation of immune signals, particularly by proliferative keratinocytes, suggesting an active role for the prolife rative keratinocyte in the pathophysiology of ACD.