The experiments described here were designed to study interactions which occur between cerebrovascular endothelial cells (EC) which comprise the blood-brain barrier (BBB) and peripheral blood leukocytes. It was observed that murine T lymphocytes capable of transferring experimental allergic encephalomyelitis (EAE) adhered to monolayers of murine cerebrovascular EC. Treatment of murine EC cultures with interferon- gamma (IFN), interleukin-1 (IL-1) and/or tumor necrosis factor-alpha (TNF) up-regulated adhesion in a time- and dose-dependent manner. Pretreatment of EC with transforming growth factor-beta (TGF) partially inhibited T cell adhesion to untreated EC and down-regulated the effects of the aforementioned cytokines on adhesion, It was also observed that peripheral blood monocytes from normotensive (WKY) and spontaneously hypertensive (SHR) rats adhered to syngeneic cerebrovascular EC. Treatment of rat EC cultures with IFN, IL-1, TNF, LPS, PMA and A23187 up- regulated adhesion in a time- and dose-dependent manner. The relative degree of enhancement was greater on SHR EC than WKY EC. The results indicate that these cytokines/factors can regulate EC-leukocyte interactions which may result in permeability changes or conversion of endothelium to a procoagulant surface at the site of the BBB. Such changes may lead to local thrombosis/hemorrhage which is characteristic of disorders such as atherosclerosis or stroke or they may affect peripheral immune cell egression into the CNS, which is a pathologic hallmark of neuroimmune disorders such as EAE and multiple sclerosis (MS). Murine cerebrovascular EC were also shown to synthesize and release prostacyclin (PGI2) upon treatment with the cytokine IL-1. The ability of peripheral immune macrophages (MO) to release IL-1, the consequent stimulation of EC-derived PGI2, as well as the inhibition of antigen (MBP)-specific proliferation of encephalitogenic T cells by PGI2 were characterized.
