CYTOKINE-MEDIATED ACTIVATION OF CULTURED CNS MICROVESSELS - A SYSTEM FOR EXAMINING ANTIGENIC MODULATION OF CNS ENDOTHELIAL-CELLS, AND EVIDENCE FOR LONG-TERM EXPRESSION OF THE ADHESION PROTEIN E-SELECTIN

Much of what is known of endothelial responses to cytokines has been d erived from in vitro studies using cultured human umbilical vein endot helial cells (EC). Less is known of CNS EC responses and whether intac t endothelium responds similarly to cultured cells. We have used techn iques by which rat CNS microvessels can be isolated, then cultured in vitro, to study the response of intact endothelium to activation with cytokines. These microvessels are composed of viable EC and perivascul ar cells, predominantly pericytes. Expression of EC activation antigen s in multicellular systems such as cultured microvessels can be assess ed quantitatively using immunofluorescence laser cytometry. Interferon gamma increased immunologically reactive major histocompatibility com plex class II antigens (<300 to 2,398 +/- 225 average fluorescence int ensity), while tumor necrosis factor alpha induced an increase in vasc ular cell adhesion molecule-1 (2,167 +/- 171) and E-selectin (1,628 +/ - 315). CNS EC appeared to respond similarly to cultured EC with the e xception that E-selectin expression was not transiently expressed but was maintained by microvessel EC for 24 and 48 h. Cultured CNS microve ssels provide a good system for studying EC activation.