Matrix adherence of endothelial cells attenuates immune reactivity: induction of hyporesponsiveness in allo- and xenogeneic models

Endothelial integrity regulates vascular tone, luminal patency, and the immune reactivity to tissue grafts. Endothelial dysfunction is the first marker and site of disease initiation and severity. It has long been known that endothelial biochemical function is density dependent, and we have recently shown that endothelial immunobiology is anchorage dependent. Matrix-embedded endothelial cells (EC) establish a controlled anchorage state and are not only immune protected but also induce a system immune protective state. We now define this aspect of vascular and immune biology in detail. The in vitro immune response of allogeneic splenocytes (proliferation, lytic activity, and cytokine expression) on exposure to aortic EC was significantly reduced if EC were embedded within three-dimensional collagen matrices (3D-EC; P<0.005) to an even greater extent than EC that had reached confluence as monolayers on tissue culture plates (EC-TCPS). Splenocyte reactivity was enhanced with repeated exposure to EC-TCPS but ...