Letter to the Editor

Journal of Investigative Dermatology (1999) 113, 139–140; doi:10.1046/j.1523-1747.1999.00643.x

SCF-KIT Pathway in Human Epidermal Melanocyte Homeostasis

B Jack Longley and Eric L Carter

Columbia University College of Physicians & Surgeons, New York, New York, USA

Correspondence: Dr J. Longley, Section of Dermopathology, College of Physicians and Surgeons of Columbia University, 630 West 168 Street, VC 5-578, New York, NY 10032

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To the Editor:

In the August issue of the Journal of Investigative Dermatology,Grichnik et al. (1998) demonstrated the responsiveness of adult human melanocytes to stem cell factor (SCF) in vivo. We have been interested in the role of SCF in postnatal skin since we discovered the production of SCF by human keratinocytes, and noted that the presence of the soluble form of SCF is associated with locally increased pigment production in the epidermis of patients with urticaria pigmentosa (Longley et al. 1993). These observations first implicated local production of SCF in postnatal melanocyte function. We agree withGrichnik et al. (1998) that their current findings are further evidence of the fundamental role played by the SCF-KIT pathway in the regulation of melanocyte proliferation and differentiation in human postnatal skin.

We would like to take this opportunity, however, to focus discussion on the difference between the role of soluble SCF, studied byGrichnik et al. (1995) and colleagues (Costa et al. 1996;Grichnik et al. 1998), and the role of membrane-bound keratinocyte-associated SCF. The majority of the immunoreactive SCF found in normal human skin is bound to keratinocyte cell membranes rather than being present in a soluble form, as originally observed by us (Longley et al. 1993) and confirmed by others (Hamann et al. 1995). Membrane-bound SCF and soluble SCF have different effects on cells (Toksoz et al. 1992;Miyazawa et al. 1995), so the distinction may be important in vivo. In particular, based on the following observations it appears that soluble SCF is insufficient to support the normal migration and maintenance of melanocytes in the skin.

Sl/Sld mice, whose cells produce only soluble SCF, are white and have no melanocytes in the epidermis or hair follicles, indicating that the soluble form of the molecule is incapable of supporting melanocyte development and function (Silvers 1979;Anderson et al. 1990).

In normal mice, the gene for SCF is expressed in the epidermis during development but not postnatally (Yoshida et al. 1996). Consequently, the number of melanocytes (and melanoblasts) present in the epidermis declines rapidly in the first few days after birth, so that essentially no melanocytes are present in the interfollicular epidermis of the adult mouse (Hirobe 1984). The color of the adult mouse therefore is a product of melanocytes that are active in the hair follicles rather than the epidermis, which lacks melanocytes and is unpigmented. This situation differs markedly from human skin, in which epidermal keratinocytes express SCF and melanocytes are maintained postnatally. We have recently demonstrated the dominance of the membrane-associated form of SCF using transgenic mice that express SCF in the basal layer of the epidermis (Kunisada et al. 1998a). These studies show that the membrane-bound form of SCF is required for melanocyte survival in the epidermis, and that its expression in murine epidermis results in the population of the epidermis by melanocytes. Thus, epidermal membrane-bound SCF is both sufficient and necessary for normal melanocyte function in the epidermis. Soluble SCF, it appears, is associated with hyperfunction of melanocytes.

Also of relevance to the work ofGrichnik et al. 1996,1998 are studies using similar strains of the transgenic mice (Kunisada et al. 1998b), which point to the presence of a cutaneous melanocyte 'stem cell' that, in mice, is not dependent on activation of KIT. Whether these cells do not express the KIT receptor or are merely not dependent on KIT activation for survival remains to be determined experimentally; however, it would be interesting to know whether the KIT-positive, TRP-1-negative cells described byGrichnik et al. (1996) are dependent on KIT for their survival. One might expect to find melanocyte stem cells in the hair follicles of normal mice, because there is no indication that melanocyte stem cells are present in the interfollicular epidermis of nontransgenic mice.

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References

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