Lipopolysaccharide (LPS) is an outer membrane glycolipid component of gram-negative bacteria known for its fervent ability to activate monocytic cells, and for its potent proinflammatory capabilities. In addition, LPS triggers the release of cytokines, chemokines as well as cell-cell adhesion molecules. We postulate that LPS may also affect the expression of matrix-binding integrin receptors, thereby modulating cell adhesive functions in monocytic cells. To test this hypothesis, we investigated the effects of LPS on the expression of the integrin 51, a fibronectin receptor, in a human monocytic cell line (U937) as well as in isolated human peripheral blood mononuclear cells (PBMC). We found that LPS increased the expression of 51 receptors, and enhanced the adherence of U937s and PBMCs to fibronectin-coated surfaces which was blocked by anti-51 antibodies. LPS increased 5 subunit mRNA accumulation in a dose- and time-dependent manner. The induction by LPS occurred, at least in part, at the level of gene transcription as indicated by experiments using 5 intact and deletion promoter constructs. The LPS-induced5 gene transcription was associated with the rapid induction of cPKC protein and activity, was blocked by protein kinase C inhibitors, and was mimicked by Lipid A. Finally, we found that an anti-CD14 antibody was able to inhibit the LPS response. Overall, the data suggest that LPS stimulates 5 gene transcription via CD14 and protein kinase C dependent signals to enhance the expression of functional 51 receptors in monocytic cells. This process may help stimulate monocytic cell activation and facilitate their migration into fibronectin-containing tissues during infection.