TNFα Induces E-Selectin Expression and PECAM-1 (CD31) Redistribution in Extracutaneous Tissues

We evaluated the experimental utility of short-term organ culture to assess cytokine-dependent endothelial activation in extracutaneous tissues. Effects of tumor necrosis factor-alpha (TNFα) on E-selectin and platelet-endothelial cell adhesion molecule-1 (PECAM-1) were assessed immunocytochemically in tissue derived from human gastrointestinal tract, female genital tract, breast, lung, kidney, and skin. Normal vessels in control explants from these sites did not stain for E-selectin and expressed PECAM-1 uniformly along plasma membranes of lumenal endothelial cells. Cytokine-stimulated vessels in explants exposed to TNFa for 6 hours revealed marked induction of E-selectin and redistribution of PECAM-1 to interendothelial junctions. PECAM-1 redistribution was also confirmed in situ using Type I skin allergic reactions in which mast cell TNF is presumably released. As in cytokine-stimulated skin, E-selectin expression in extracutaneous tissues was restricted to postcapillary venules, although anastomotic junctions between capillaries and venules were more clearly defined at extracutaneous sites. These data establish short-term organ culture as a potentially useful means of assessing endothelial activation in extracutaneous tissues.