Expression and inducibility of vascular adhesion receptors in development

ICAM-1 and VCAM are cell adhesion receptors expressed on vascular endothelial cells, and their expression is up-regulated as part of the inflammatory response. Tumor-derived Py-4-1 cells were a source of murine endothelial cells, and they showed increased lymphocyte binding when incubated with TNF alpha. Py-4-1 cells stimulated with TNF alpha or LPS also had elevated levels of ICAM-1 and VCAM RNAs, with maximum levels at 2 h. Developmental expression of adhesion receptors was assayed in murine yolk sacs and in cystic embryoid bodies (CEBs) that differentiate in vitro from murine embryonic stem cells. ICAM-1 and VCAM RNAs were expressed in unstimulated yolk sacs and CEBs. Expression was inducible in CEBs by exposure to LPS at all developmental stages, beginning at day 6. The time course of RNA induction in CEBs was similar to that of the Py-4-1 endothelial cell line. ICAM-1 protein expression was localized to vascular and hematopoietic blood islands in the CEBs. These results show that embryonic cells respond to inflammatory mediators by up-regulating expression of vascular adhesion receptors, and they imply an early ontogeny for the endothelial cell signal transduction pathway necessary for leukocyte recruitment.