Tenascin is overexpressed in vitiligo lesional skin and inhibits melanocyte adhesion

Abstract

SummaryThe aetiology of vitiligo remains obscure. In this study, the role of integrins in the observed inability of melanocytes to repopulate lesional skin was investigated. Antibodies directed to a 2 , a 3 , a 5 , a v , a 6 , b 1 and b 3 integrin subunits were used. Immunohistology revealed no marked differences in the overall levels of expression of integrins between control, non-lesional, perilesional or lesional skin. Moreover, no differences were noted in the level of expression of integrins or the adhesive capacity between cultured control cells derived from three separate donors and vitiligo-derived melanocytes from two donors. Rather, it was clearly observed that towards the lesion, vitiligo skin contains increasing amounts of tenascin in the basal membrane and papillary dermis in five patients employing T2H5 antihuman tenascin antibody. The anti-adhesive effect observed in vitro for this extracellular matrix molecule using normal melanocytes may contribute to loss of pigment cells in vitiligo or to ineffective repopulation of the lesions.In vitiligo, melanocytes are gradually lost in depigmenting lesions of the skin. 1 It has been suggested that defective adhesion is involved in loss of melanocytes in this pigmentary disorder. 2 Moreover, the persistence of depigmented lesions is suggestive of defective melanocyte migration which may be reversed by photochemotherapy, 2 and therefore baseline expression of adhesion molecules may differ in vitiligo as compared with control skin. Melanocyte adhesion, spreading and migration is mediated by integrins. 3 Employing antibodies to integrin subunits, the specific integrins involved in each process have been identified in vitro. 3,4 Importantly, all integrins thus far identified on melanocytes can also be found on neighbouring keratinocytes. Although immunohistology has been employed to identify integrins expressed on melanocytes in situ per se, 3 this may not be the method of choice to determine differences in the level of expression by melanocytes. Even by double immunostaining procedures, it is difficult to distinguish between integrin expression by melanocytes vs. neighbouring keratinocytes. Therefore, in vitro cultures derived from control as well as from vitiligo non-lesional skin were employed to investigate further potential differences in adhesive behaviour in vitiligo and control skin. In addition, the use of cultured cells provides the opportunity to perform functional adhesion assays. In this respect it is of great interest to note that cultured melanocytes from nonlesional vitiligo skin appear to retain disease-related characteristics. It has been demonstrated that vitiligo melanocytes have altered growth characteristics under limiting conditions. 5 Moreover, upon electron microscopic observation, dilated rough endoplasmic reticulum (RER) is apparent in diseased cells from human and mouse vitiligo subjects. 6,7 Therefore, the use of cultured cells to investigate differences in adhesive characteristics is justified.The level of expression of relevant i...

A Critical Appraisal of Vitiligo Etiologic Theories. Is Melanocyte Loss a Melanocytorrhagy?

“…An increased amount of tenascin has been detected in the basal membrane and in the papillary dermis. Le Poole et al suggest that this extracellular matrix molecule, which inhibits adhesion of melanocytes to fibronectin, may contribute to the loss of pigment cells in vitiligo (77). The origin of the deposits of tenascin are unclear but one may also speculate that cytokines produced as a consequence of local immune reactivity may contribute to this finding.…”

Vitiligo: A comprehensive overview

“…184 Tenascin, an extracellular matrix molecule which inhibits adhesion of melanocytes to fibronectin, is elevated in vitiliginous skin, and may contribute to loss of melanocytes or ineffective repopulation. 185 …”

The Pathogenesis of Vitiligo

“…In general, the vitiligo patients were found to express higher levels of tenascin compared to controls. Whether the increased tenascin expression is a cause or consequence of vitiligo is unclear; however, from these results it is arguable that modified cellular adhesion is evident in vitiligo and could contribute to its pathogenesis (Le Poole et al, 1997). A pivotal study regarding the melanocytorrhagy hypothesis investigated how trauma could elicit vitiligo lesions, a process also called the Koebner phenomenon.…”

“…This demonstrates that MCHR1-binding autoantibodies can block the function of MCHR1, and MCHR1 is a relevant B-cell auto-antigen in vitiligo (Gottumukkala et al, 2006). Le Poole et al (1996) sought to elucidate what specific types of immune mechanisms were taking place in vitiligo. The perilesional skin of patients suffering from inflammatory vitiligo was evaluated.…”