Selective down-regulation of the alpha6-integrin subunit in melanocytes by UVB light.
In vivo, melanocytes bind to laminin (LM) molecules of the basement membrane (BM) via the integrins alpha3beta1 and alpha6beta1, and they adhere to neighbouring keratinocytes via E-cadherin. Only few studies have addressed the impact of ultraviolet (UV) light on the interaction of melanocytes with their microenvironment. In this report, we examined the influence of UVB irradiation on the expression of the most important melanocyte-adhesion molecules (E-, N-cadherin, alpha2-, alpha3-, alpha5-, alpha6-, alphaV-, beta1-, beta3-integrins and ICAM-1) in vitro by flow cytometry. We were able to demonstrate that the alpha6-integrin subunit is selectively and reversibly down-regulated by UVB in a dwzm 150ose-dependent manner. In comparison, keratinocytes lacked UVB-inducible alterations in the expression of alpha6-integrin. In the presence of LM-1, the UVB-induced down-regulation of alpha6-integrin in melanocytes was significantly reduced. Moreover, LM-1 increased the resistance of melanocytes to UVB-induced cell death, as measured by annexinV-binding analysis. This effect was reversed by preincubation with an alpha6-integrin-blocking antibody. By immunofluorescence, we could demonstrate that UVB leads to a dose-dependent internalization of alpha6-integrin, providing an obvious explanation for the down-regulation on the outer cell surface observed by flow cytometry. We suggest that adhesion to LM-1 through alpha6-integrin represents a protective mechanism for melanocytes to withstand UVB damage. Through alpha6-integrin internalization, sunburns might alter the interaction between melanocytes and the BM, resulting in apoptosis induced by loss of anchorage (anoikis). Repeated sunburns may then lead to the selection of a population of melanocytes which are capable of anchorage-independent survival, culminating in solar nevogenesis and melanoma development.
Krengel
Sven
S
Department of Dermatology, University of Lübeck, Lübeck, Germany. svenkrengel@gmx.net
Stark
Imke
I
Geuchen
Christian
C
Knoppe
Bettina
B
Scheel
Gabriele
G
Schlenke
Peter
P
Gebert
Andreas
A
Wünsch
Lutz
L
Brinckmann
Jürgen
J
Tronnier
Michael
M
D017304:Annexin A5 / Q000494:pharmacology; D017209:Apoptosis; D002448:Cell Adhesion; D002470:Cell Survival; D002478:Cells, Cultured; D015536:Down-Regulation; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006801:Humans; D039503:Integrin alpha6 / Q000737:chemistry*; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D007797:Laminin / Q000378:metabolism*; D008544:Melanocytes / Q000166:cytology / Q000378:metabolism* / Q000528:radiation effects; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D011485:Protein Binding; D013997:Time Factors; D014466:Ultraviolet Rays
D017304:Annexin A5; D039503:Integrin alpha6; D007797:Laminin; C121346:laminin 1