Stimulation of Human and Murine Adherent Cells by Bacterial Lipoprotein and Synthetic Lipopeptide Analogues

Abstract Lipoprotein from the outer membrane of Escherichia coli and its synthetically prepared N-terminal lipopeptide segments Pam 3 Cys-Ser-Ser-Asn-Ala and Pam 3 Cys-Ser, as well as lipo-protein from other Enterobacteriaceae , constitute potent polyclonal B lymphocyte activators. Here, we demonstrate that these compounds were also able to stimulate human and murine leukocytes: in murine macrophages, we could show the induction of interleukin 1 release by the mitogens, as measured in the thymocyte proliferation assay. Moreover, murine peritoneal exudate cells were stimulated to secrete prostaglandins E2 (PGE 2 ) and F2 α (PGF 2α ). The effect of Pam 3 Cys-Ser on the murine macrophage cell line P388D 1 was also tested: the compound induced an increase in proliferation, as measured by a thymidine incorporation assay. In addition, the cell line could be induced to release IL 1 into the supernatant. Correspondingly, induction of IL 1 release could also be demonstrated in human mononuclear cells. Our results demonstrate that the two novel synthetic lipopeptides are potent stimulators for human monocytes and murine macrophages. These findings may be important for the elucidation of the role of these bacterial surface components in the course of bacterial infections.