Heterogeneity of dermal microvascular endothelial cell antigen expression and cytokine responsiveness in situ and in cell culture.

Abstract

Microvascular endothelial cells (EC) recruit circulating leukocytes at sites of inflammation, in part through cytokine-regulated expression of endothelial-leukocyte adhesion molecules. Adhesion molecule expression varies among vascular beds and among EC within microvessels of a particular vascular bed. In the present study, we have examined the patterns of antigen expression and cytokine responsiveness of dermal microvascular endothelial cells (DMEC) in a skin organ culture model and, for comparison, in cell culture. Within the superficial vascular plexus (SVP) of normal skin, CD36 molecule expression is undetectable on capillary loops and is expressed on DMEC in only 20% of the larger, horizontal vessels. CD36 expression is not modulated by cytokines. Endothelial-leukocyte adhesion molecule-1 (ELAM-1) expression induced at 6 and 24 h by TNF or IL-1, is restricted to the venular side of the capillary 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 by TNF, IL-1, or IL-4, alone or in combination at either time point. When inflamed skin is examined in organ culture, SVP EC are cytokine responsive 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 inducible by TNF, IL-1, and/or IL-4 on capillaries and larger microvessels 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 (mean 75%) in seven separate isolates and is not modified by cytokines. Upon 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 expression is negligible at both times. These results with DMEC differ from human umbilical vein EC analyzed in parallel, which are completely CD36- and show transient ELAM-1 and sustained VCAM-1 expression in response to TNF and IL-1. In summary, we have demonstrated that DMEC comprise a heterogeneous population that differ from umbilical vein EC.