INDUCIBILITY AND EXPRESSION OF MICROVASCULAR ENDOTHELIAL ADHESION MOLECULES IN LESIONAL, PERILESIONAL, AND UNINVOLVED SKIN OF PSORIATIC PATIENTS

Previous studies have demonstrated 1) that patterns of inducible endot helial cell expression of endothelial leukocyte adhesion molecule-1 (E LAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in response to c ytokines varies both with anatomic position within the dermal microvas culature and with the presence of perivascular inflammatory infiltrate s, and 2) that the anatomic architecture of the dermal superficial ple xus (SVP) is altered in inflamed lesional but not in uninvolved skin o f psoriatic patients. The present study was designed to evaluate the p attern of cytokine inducibility of ELAM-1 and VCAM-1 in altered dermal microvessels of psoriatic patients. At the light microscope level, pr eculture biopsies of uninvolved and perilesional skin were indistingui shable by morphology and ELAM-1 and VCAM-1 expression were virtually a bsent. In contrast, biopsied lesional skin showed elongated capillary loops and increased numbers of T cells compared to uninvolved and peri lesional skin. The dermal microvasculature of the SVP of lesional skin contained ELAM-1(+) in 29.4% of vessels and VCAM-1(+) endothelial cel ls in 8.7% of vessels. After 24 h of organ culture in medium supplemen ted with tumor necrosis factor and interleukin-4, ELAM-1(+) endothelia l cells in the SVP were increased significantly in uninvolved (from me an 0.5% to 27% of vessels), perilesional (from mean 5.5% to 41.8% of v essels), and lesional skin (from mean 29.4% to 45.7% of vessels). VCAM -1 was not inducible on SVP endothelial cells in uninvolved skin but V CAM-1(+) endothelial cells were increased significantly in perilesiona l (from mean 0.7% to 23.7% of vessels) and lesional skin (from mean 8. 7% to 41.4% of vessels). In uninvolved and perilesional skin ELAM-1 an d VCAM-1 were confined to endothelial cells below the rete. In contras t, endothelial cells of the intrapapillary part of the capillary loop of lesional skin became cytokine responsive, in that ELAM-1 and VCAM-1 could be induced at this site. By immunoelectron microscopy, expressi on was most intense on the luminal surface of venular endothelial cell s and at the interendothelial junctions. In conclusion, we have presen ted evidence that the cytokine responsiveness of microvascular endothe lial cells is altered in psoriasis in a pattern that may explain both the circumscribed nature and the epidermal involvement of the psoriati c plaque.