Biologie moléculaire du mélanocyte humain normal

Abstract

The past decade has brought a great deal of new knowledge on the biology of normal human melanocytes. The capacity to propagate these normal cells in vitro has opened vast opportunities for studying the proliferation and differentiation of melanocytes. At present, different culture systems are being employed, but in general terms the following classification can be made on the known mitogens for normal human melanocytes : (1) phorbol esters (TPA), probably working through a down- regulation of PKC ; (2) cAMP inducers such as cholera-toxin, IBMX, dbcAMP and possibly LTC-4 ; (3) peptide growth factors : bFGF is presumed to be the natural growth factor for melanocytes. The cellular physiology of the interaction between ultraviolet radiation (UVR) and the epidermal melanocyte still has many unknowns. A direct pigmentogenic response of melanocytes to UVB in vitro has been demonstrated, but, contrary to the in vivo situation, this was accompanied by a dose-dependent inhibition of melanocyte proliferation. UVR probably also works through keratinocytes to stimulate melanogenesis and melanocyte proliferation, and keratinocytic bFGF is a good candidate for being a paracrine factor to melanocytes. The second messengers responsible for transducing the UVR stimulus also are a hot point of investigation, and it seems that both the cAMP and PKC-pathway could be involved. Keratinocytes play an important role in determining melanocyte morphology, and NGF could be an important paracrine factor in this respect. The importance of cytoskeletal rearrangements during dendrite formation seems established. The master role of keratinocytes in determining the melanocyte/keratinocyte ratio in the epidermis has been demonstrated very elegantly using skin equivalent models. Recent evidence seems to indicate that the melanocyte could be of importance in immunological reactions as well.