Interleukin 1-induced lymphocyte binding to endothelial cells. Role of cAMP as a second messenger.

Interleukin 1 (IL 1) is a potent protein mediator of inflammation. Among other things it increases the number of lymphocytes adhering to endothelial cell monolayers. We analyzed the signal transduction during IL 1-induced lymphocyte binding. Dibutyryl cyclic AMP, which is a cAMP analog able to penetrate into the cytosol, increased lymphocyte binding to the same extent as IL 1. Direct activation of adenylate cyclase by forskolin enhanced also lymphocyte binding. IL 1 increased the level of cytosolic cAMP in a time- and dose-dependent manner measured with radioimmunoassay. 2',5'-Dideoxyadenosine, which is an inhibitor of adenylate cyclase, decreased both the IL 1-induced lymphocyte binding to endothelial cells and elevation in cytosolic cAMP levels. Lymphocyte binding increased with cytosolic cAMP levels in accordance with elevation of IL 1 concentration. These results suggest that cAMP is essential in signal transduction during IL 1-induced lymphocyte binding to cultured endothelial cell monolayers.