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

• DOI: 10.1096/fj.06-7051com
• Publication Date: 2007-02-02T19:37:01Z
• Authors: Heiko Methe; Adam Groothuis; Mohamed H. Sayegh; Elazer R. Edelman
• Keywords: Splenocyte

ABSTRACT Endothelial integrity regulates vascular tone, luminal patency, and the immune reactivity to tissue grafts. dysfunction is first marker site of disease initiation severity. It has long been known that endothelial biochemical function density dependent, we have recently shown immunobiology anchorage dependent. Matrix‐embedded cells (EC) establish a controlled state are not only protected but also induce system protective state. We now define this aspect biology in detail. The vitro response allogeneic splenocytes (proliferation, lytic activity, cytokine expression) on exposure aortic EC was significantly reduced if were embedded within three‐dimensional collagen matrices (3D‐EC; P < 0.005) an even greater extent than had reached confluence as monolayers culture plates (EC‐TCPS). Splenocyte enhanced with repeated EC‐TCPS minimally preexposed 3D‐EC (P< 0.002). induced differentiation into CD4 + CD25 Foxp3 regulatory T 0.02). potential effect subsequent confirmed vivo. Repeated immune‐competent mice injections xenogeneic vigorous host immunity. In contrast, prior implantation hyporesponsiveness toward injection humoral response, decreased lower frequency effector 0.001). interaction its matrix determines phenotype, viability, biosecretory potential. show microenvironmental influences endothelial‐mediated activation allo‐ cells. 3D matrix‐embedding limits ability initiate adaptive immunity, initial confers immunogeneic EC. These effects transcended traditional control imposes reflects perhaps higher order control. Our findings might offer novel insights endothelialmediated diseases cell‐based therapies.—Methe, H., Groothuis, A., Sayegh, M. Edelman, E. R. Matrix adherence attenuates reactivity: induction models. FASEB J. 21, 1515–1526 (2007)