Investigation On Immunological Characteristics Of Human Melanocytes And Effects Of Aloesin On Melanogenesis And Related Gene Expressions Of Melan-a

Investigation on immunological characteristics of human melanocytes and Effects of Aloesin on melanogenesis and related gene expressions of Melan-aThe biology and physiology of melanocytes have long been studied due to their function as unique professional melanin producing cells in human skin. Pigmentation disorders will certainly occur if the biochemistry or enzymology of melanin synthesis is interrupted (1-2). Nevertheless, melanocytes are also morphologically highly dendritic, and their central localization at the basal layer of the epidermis raises the possibility that they are immunologically important. Most knowledge about the immunologic characteristics of melanocytes comes from the pathogenesis and therapeutic research of vitiligo and melanoma in which they are always passively taken as target cells. The presence of anti-melanocyte antibodies may play particularly important roles in the etiology of vitiligo. IgG anti-melanocyte antibodies (V-IgG) were found to induce melanocyte damage in vitro by a complement-mediated mechanism and by antibody-dependent cellular cytotoxicity (3). However, liters of such autoantibodies in individuals with melanoma-associated hypopigmentation are similar to those in normal controls, suggesting that, in these patients, another mechanism may lead to melanocyte loss (4). The observation that melanocyte proteins are targets for antimelanoma CTLs suggests that destruction of epidermal melanocytes in vitiligo patients could be due to a melanocyte-specific CTL response (5-8). The histology of advancing margins of vitiligo reveals a lymphocytic infiltratepredominantly composed of CD8+ T cells expressing the skin homing receptor, cutaneous lymphocyte-associated antigen (CLA), which is a modified form of P selectin-binding glycoprotein, and the majority of these T cells also express the cytotoxic effector molecules perform and Granzyme (9-11). Moreover, dendritic cell-based vaccination strategies for treatment of melanoma have been accompanied by the acquisition of tumor specific CTL responses and cutaneous depigmentation (12). Further, when a patient with metastatic melanoma was infused with Melan-A-specific CD8+ T cells, this patient developed inflammatory skin lesions and depigmented spots that were associated with the local presence of these T cell clones (13). These results above strongly suggest that melanocyte-specific CTLs can play a role in melanocyte destruction.Previous studies show that melanocytes can express major histocomptibility complex (MHC)-class I and II molecules and that adhesion molecules such as intercellular adhesion molecule (ICAM)-l and vascular cell adhesion molecule (VCAM)-1 (14-16). In addition, they can produce several cytokines, such as interleukin (IL)-l, IL-6, IL-8 and transforming growth factor-pl(TGF-pl) (17-20). To our surprise, melanocytes are capable of phagocytosis and can even process antigens and present antigenic peptides to T lymphocytes. Melanocytes that present peptides from the 65-Kd heat shock protein (HSP)of Mycobacterium leprae not only induce costimulatory signal dependent T lymphocyte proliferation, but also become the target of these cytotoxic T cell clones (21). These studies indicate that melanocytes are nonprofessionalantigen-presenting cells (APC), which may lead to a new hypothesis on those immunologically related pigmentary disorders involving melanocyte destruction. In this regard, it is of great importance to first identify melanocyte surface antigens and it may allow the possibility of a further exploration of the immune functions of melanocytes. Herein we report some essential immunologic markers on cultured melanocytes. Most importantly we found that melanocytes functionally express CD40, a hot molecule involved in cellular immune response, which is closely related to their capacity to stimulate T lymphocyte proliferation and cytokine secretion. In Part I, we demonstrated that cultured melanocytes express low levels of some immunologically important surface markers such as ICAM-1 and CD40. Moreo...