ENDOTHELIAL-CELLS AND EXTRACELLULAR CALMODULIN INHIBIT MONOCYTE TUMOR-NECROSIS-FACTOR RELEASE AND AUGMENT NEUTROPHIL ELASTASE RELEASE

Cultured human umbilical vein endothelial cells inhibited tumor necros is factor-alpha release from whole blood or isolated mononuclear cells exposed to endo toxin. In contrast, the endothelial cells augmented n eutrophil elastase release in the same blood. A protein with these fun ctional properties was isolated from endothelial cell-conditioned medi a and, surprisingly, was identified as calmodulin. Authentic calmoduli n mimicked the effect of endothelium. I-125-Calmodulin bound to a high affinity site on monocytic cell lines (K-d similar to 30 nM, in agree ment with its functional activity). Cross-linking of I-125-calmodulin to monocytic cells identified a candidate calmodulin receptor. We conc lude that calmodulin possesses an extracellular signaling role in addi tion to its intracellular regulatory functions. Calmodulin released at sites of tissue injury or possibly by specific mechanisms in the endo thelium can bind to receptors, modulating the activities of inflammato ry cells.