CAMs in the Skin

ICAM-1 is an 85- to 110-kDa transmembrane glycoprotein mapped to human chromosome 19 and constitutively expressed by a variety of cells. Binding of ICAM-1 to its ligand, lymphocyte function-associated antigen 1, is the major pathway for kera-tinocytes and Langerhans' cells to interact with leukocytes and mediates both antigen-independent and antigen-dependent adhesion (Trefzer and Krutmann 1995). In addition, ICAM-1 has been shown to function as a receptor for human rhinoviruses ("common cold") (Greve et al. 1989, Staunton et al. 1989) and as an endothelial cell receptor for Plasmodium falciparum in malaria (Behrendt et al. 1989).

Keratinocytes normally express no or minimal ICAM-1, and this is regulated at the transcriptional level (Norris 1995). ICAM-1 can be induced or up-regulated by cytokines such as TNF-a, IL-1, and IFN-y (Dustin et al., 1986) and by TNF-p (Krutmann et al. 1990, 1991). The responsiveness to cytokines that induce ICAM-1 transcription differs between tissues (Cornelius et al. 1993,1994). An example of this different responsiveness is that IL-1 induces ICAM-1 on endothelial cells but, although debated, probably not on keratinocytes (Norris 1995, Trefzer and Krutmann 1995). ICAM-1 expression induced by TNF-a and IFN-y is maximal in basal, undifferenti-

ated keratinocytes. IFN-y from dermal inflammatory cells and histamine from dermal mast cells are thought to influence basal ICAM-1 expression (Norris 1995).

Expression of CAMs on endothelial cells is essential for leukocyte margination, rolling, adhesion, and emigration from the bloodstream into tissue (Butcher 1991, Butcher et al. 1986, Shimizu et al. 1992).

VCAM-1 is minimally expressed on resting endothelial cells, but it is expressed by various cell types on activation. IL-1 and TNF-a but not UV light induces VCAM-1 on endothelial cells. The receptor for VCAM-1 is VLA-4 on monocytes and lymphocytes (Norris 1993).

E-selectin (115 kDa) is one of three proteins in the selectin family encoded on the long arm of human chromosome 1. E-selectin is only expressed by activated postcap-illary venules (Rodhe et al. 1992) and shows specificity for skin homingT cells (Picker et al. 1991, Zimmerman et al. 1992).

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