Peripheral Lymph Node Addressins are Expressed on Skin Endothelial Cells

Abstract

The term "peripheral node addressins" describes a set of several endothelial adhesion molecules, which collectively bind to L-selectin and react with monoclonal antibody MECA-79. They regulate lymphocyte recirculation through peripheral nodes. Their expression is thought to be restricted to a specialized vascular segment within the node, called the high endothelial venule. In certain chronic skin diseases, however, postcapillary venules of the skin may also acquire a high endothelial venule-like morphology. Employing immunohistochemistry on cryostat sections, we found these skin endothelial cells - like peripheral node high endothelial venules - to be reactive with monoclonal antibody MECA-79. Tissue lysates from the same specimens were then analyzed by immunoprecipitation using recombinant human L-selectin Fc-chimeras followed by immunoblotting using monoclonal antibody MECA-79. In contrast to peripheral node endothelium, which mainly expressed peripheral node addressin moieties of molecular sizes 90-110 kDa and 160 kDa, endothelial cells in cutaneous T cell lymphoma skin lesions expressed an additional and not yet defined 220 kDa peripheral node addressin-like molecule. Most surprisingly, even in normal skin specimens, we found a distinct subset of endothelial cells located around hair follicles constitutively expressing 90-110 kDa peripheral node addressin-like moieties. It is intriguing to speculate that - in analogy to the role of peripheral node addressins in peripheral nodes - the induced expression of peripheral node addressins in chronic T cell mediated skin diseases is responsible for a sustained lymphocyte recruitment. The constitutive expression of peripheral node addressins on perifollicular endothelium may serve for a continuous lymphocyte recirculation through normal skin.