POLYINOSINIC - POLYCYTIDYLIC ACID IS A POTENT ACTIVATOR OF ENDOTHELIAL-CELLS

Polyinosinic:polycytidylic acid (poly I:C) is a synthetic double-stran ded polyribonucleotide that elicits immune responses analogous to thos e observed during viral infection. It is also known to modulate the ex pression of certain autoimmune disorders including diabetes mellitus i n the BB rat and NOD mouse. The mechanisms underlying these immunomodu latory effects is not known, but it could involve activation of vascul ar endothelium. We now report that parenteral poly I:C induces rat pan creatic endothelium to hyperexpress intercellular adhesion molecule 1 (CD54). This is accompanied by a perivascular recruitment of mononucle ar cells to the exocrine pancreas. Corollary in vitro studies demonstr ated that poly I:C is a potent activator of both rat and human endothe lial cells in culture. It upregulates endothelial expression of severa l leukocyte adhesion molecules, stimulates the release of interleukin- 6 and interleukin-8, and antagonizes interfron-gamma induction of majo r histocompatibility complex class II expression. We conclude that pol y I:C activates endothelial cells to express surface molecules and cyt okines in a pattern classically associated with leukocyte recruitment. These effects may in part contribute to the immunomodulatory effects of poly I:C in animal models of autoimmunity.