Stimulation of human endothelial cells by synthetic muramyl peptides: production of colony-stimulating activity (CSA).

The in vivo induction of colony-stimulating activity (CSA) by well-defined immunomodulatory synthetic muramyl peptides has been demonstrated recently in mice. In the present study, we tested the capacities of three muramyl peptides to induce CSA production in human endothelial cell (HEC) cultures. Two adjuvant-active peptides (MDP and Murabutide) induced CSA in the supernatant of cultured endothelial cells, whereas an adjuvant-inactive compound had no effect. This effect of MDP and Murabutide appeared to be time and concentration dependent and was not secondary to decreased production of inhibitors of colony formation. CSA secretion by stimulated HEC required de novo protein synthesis and did not result from the release of preformed active CSA. Maximal concentration appeared in the supernatant media within the first 24 h after addition of muramyl peptides, and a substantial second CSA secretion could be observed after a subsequent 24 h reexposure. This CAS was not dialyzable and promoted granulocyte-macrophage formation of nonadherent human marrow and unfractionated murine marrow. Our data demonstrate that the human endothelial cell is a target cell for MDP and Murabutide and suggest that in vivo endothelium might play an active role in muramyl peptide-induced modulation of hematopoiesis.