HETEROGENEITY OF DERMAL MICROVASCULAR ENDOTHELIAL-CELL ANTIGEN EXPRESSION AND CYTOKINE RESPONSIVENESS IN-SITU AND IN CELL-CULTURE

Microvascular endothelial cells (EC) recruit circulating leukocytes at sites of inflammation, in part through cytokine-regulated expression of endothelial-leukocyte adhesion molecules. Adhesion molecule express ion varies among vascular beds and among EC within microvessels of a p articular vascular bed. In the present study, we have examined the pat terns of antigen expression and cytokine responsiveness of dermal micr ovascular endothelial cells (DMEC) in a skin organ culture model and, for comparison, in cell culture. Within the superficial vascular plexu s (SVP) of normal skin, CD36 molecule expression is undetectable on ca pillary loops and is expressed on DMEC in only 20% of the larger, hori zontal vessels. CD36 expression is not modulated by cytokines. Endothe lial-leukocyte adhesion molecule-1 (ELAM-1) expression induced at 6 an d 24 h by TNF or IL-1, is restricted to the venular side of the capill ary loop and to the venules proper. Vascular cell adhesion molecule-1 (VCAM-1) expression is not inducible on EC of the SVP in normal skin b y TNF, IL-1, or IL-4, alone or in combination at either time point. Wh en inflamed skin is examined in organ culture, SVP EC are cytokine res ponsive regarding VCAM-1 expression. Within the deep vascular plexus ( DVP). CD36 molecules are expressed on EC in all capillaries and small vessels. Both ELAM-1 and, to a lesser extent, VCAM-1 expression are in ducible by TNF, IL-1, and/or IL-4 on capillaries and larger microvesse ls at 6 and 24 h. The larger vessels at the dermal-subcutaneous border were found to be CD36-/ELAM-1+/VCAM-1+ after cytokine treatment. CD36 expression of DMEC in cell culture varies from 47 to 98% of cells (me an 75%) in seven separate isolates and is not modified by cytokines. U pon TNF or IL-1 activation, 50 to 90% of DMEC express ELAM-1 molecules at 6 h and expression persists at high levels for 24 h. VCAM-1 expres sion is negligible at both times. These results with DMEC differ from human umbilical vein EC analyzed in parallel, which are completely CD3 6- and show transient ELAM-1 and sustained VCAM-1 expression in respon se to TNF and IL-1. In summary, we have demonstrated that DMEC compris e a heterogeneous population that differ from umbilical vein EC.