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(American Journal of Pathology. 2002;161:763-770.)
© 2002 American Society for Investigative Pathology

Short Communication

Novel Expression of Vascular Cell Adhesion Molecule-1 (CD106) by Squamous Epithelium in Experimental Acute Graft-versus-Host Disease

Judith C. Kim*, Diana Whitaker-Menezes*, Masatoshi Deguchi*, Brigette S. Adair*, Robert Korngold{dagger} and George F. Murphy*

From the Department of Pathology,* The Jefferson Center for Dermatopathology Laboratories for Cutaneous Research, and The Kimmel Cancer Center,{dagger} Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania

Vascular cell adhesion molecule-1 (VCAM-1; CD106), the receptor for VLA-4, is an important mediator of adhesive and co-stimulatory interactions that govern cutaneous immune responses. Initial studies designed to elucidate temporal aspects of endothelial adhesion molecule induction in murine acute graft-versus-host disease (aGVHD) revealed unexpected and novel VCAM-1 expression by cutaneous and mucosal epithelial cells. Immunohistochemical techniques confirmed VCAM-1 staining as early as 7 days after transplantation in a distinctive subpopulation of squamous epithelial cells that normally occupy focal domains within the epidermal basal cell layer, the follicular infundibulum, and the dorsal lingual epithelium. Specifically, VCAM-1 expression was intimately associated with rete ridge-like prominences in footpad epidermis and in dorsal lingual epithelium. VCAM-1, as evaluated by serial section-labeling techniques, was preferentially expressed at sites of early epithelial infiltration by CD4+ T cells. Western blot analysis confirmed expression of the 110-kd isoform of VCAM-1 in epithelium isolated from aGVHD animals, and immunoelectron microscopy demonstrated VCAM-1 reactivity restricted exclusively to epithelial cell plasma membranes. It is concluded that VCAM-1 is selectively expressed by discrete squamous epithelial subpopulations in murine aGVHD. As such, VCAM-1 may play a previously unrecognized role in mediating interactions between donor effector T lymphocytes and host epithelial cell targets.


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