Vascular endothelium plays an important role in controlling communication between the immune system and tissues such as myocardium. Disturbances in this regulatory function can lead to evolution of disease processes ranging from inflammation to atherosclerosis. The initial triggers and amplification steps of adhesion are still poorly understood. Recent evidence suggests that the erbB-1 tyrosine kinase receptor can participate both in cellular adhesion, by binding to membrane-anchored forms of its ligands, and intercellular signaling in other systems. Although the effects of some soluble growth factors/cytokines on activation of endothelium and leukocytes have been described, the possibility that these factors are able to mediate cell-cell adhesion and signaling has not been investigated. We propose that members of the erbB family may participate in such interactions between leukocytes and endothelial cells. This hypothesis will be addressed in the following ways: (1) determination of the expression of erbB family receptors and their respective membrane-bound ligands on endothelial cells and leukocytes; (2) evaluation of the contribution of these molecular interactions in intercellular adhesion; and, (3) definition of the role of such interactions in pathophysiologic states involving the congener cell pairs, in vitro. Elucidation of these molecular pathways represents a novel approach to defining intercellular adhesion and signaling between these two important cell types. This will contribute to our understanding of vascular disease and may provide insight into designing molecular and pharmacologic strategies to prevent vasculopathic states.
| Russell, K S; Stern, D F; Polverini, P J et al. (1999) Neuregulin activation of ErbB receptors in vascular endothelium leads to angiogenesis. Am J Physiol 277:H2205-11 |
