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 endothelial cell expression of endothelial leukocyte adhesion molecule-1 (ELAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in response to cytokines varies both with anatomic position within the dermal microvasculature and with the presence of perivascular inflammatory infiltrates, and 2) that the anatomic architecture of the dermal superficial plexus (SVP) is altered in inflamed lesional but not in univolved skin of psoriatic patients. The present study was designed to evaluate the pattern of cytokine inducibility of ELAM-1 and VCAM-1 in altered dermal microvessels of psoriatic patients. At the light microscope level, preculture biopsies of uninvolved and perilesional skin were indistinguishable by morphology and ELAM-1 and VCAM-1 expression were virtually absent. In contrast, biopsied lesional skin showed elongated capillary loops and increased numbers of T cells compared to uninvolved and perilesional skin. The dermal microvasculature of the SVP of lesional skin contained ELAM-1+ in 29.4% of vessels and VCAM-1+ endothelial cells in 8.7% of vessels. After 24 h of organ culture in medium supplemented with tumor necrosis factor and interleukin-4, ELAM-1+ endothelial cells in the SVP were increased significantly in uninvolved (from mean 0.5% to 27% of vessels), perilesional (from mean 5.5% to 41.8% of vessels), 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 VCAM-1+ endothelial cells were increased significantly in perilesional (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 and VCAM-1 were confined to endothelial cells below the rete. In contrast, 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, expression was most intense on the luminal surface of venular endothelial cells and at the interendothelial junctions. In conclusion, we have presented evidence that the cytokine responsiveness of microvascular endothelial cells is altered in psoriasis in a pattern that may explain both the circumscribed nature and the epidermal involvement of the psoriatic plaque.
Petzelbauer
P
P
Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, Connecticut.
Pober
J S
JS
Keh
A
A
Braverman
I M
IM
D000328:Adult; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D019040:E-Selectin; D004730:Endothelium, Vascular / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008833:Microcirculation; D016253:Microscopy, Immunoelectron; D008875:Middle Aged; D011565:Psoriasis / Q000378:metabolism* / Q000473:pathology; D012867:Skin / Q000098:blood supply* / Q000473:pathology; D019010:Vascular Cell Adhesion Molecule-1
D015815:Cell Adhesion Molecules; D019040:E-Selectin; D019010:Vascular Cell Adhesion Molecule-1