The involvement of CD14 in the activation of human monocytes by peptidoglycan monomers

Background: Cell-wall components of Gram-positive and Gram-negative bacteri a induce the production of cytokines in human peripheral blood mononuclear cells. These cytokines are the main mediators of local or systemic inflamma tory reaction that can contribute to the development of innate immunity. Aims: This study was performed to analyze the involvement of CD14 molecule in the activation of human monocytes by peptidoglycan monomer (PGM) obtaine d by biosynthesis from culture fluid of penicillin-treated Brevibacterium d ivaricatum NRLL-2311. Methods: Cytokine release of interleukin (IL)-1, IL-6 and tumor necrosis fa ctor-alpha from human monocytes via soluble CD14 (sCD14) or membrane-associ ated (mCD14) receptor using anti-CD14 monoclonal antibody (MEM-18) or lipid A structure (compound 406) was measured in bioassays. Results: The results demonstrated that PGM in the presence of human serum m ight induce the monokine release in a dose-dependent manner. The addition o f sCD14 at physiologic concentrations enhanced the PGM-induced monokine rel ease, while the monokine inducing capacity of PGM in the presence of sCD14 was inhibited by MEM-18. Effects of PGM were also blocked by glycolipid, co mpound 406, suggesting the involvement of binding structures similar to tho se for lipopolysaccharide. Conclusion: Activation of human monocytes by PGM involves both forms of CD1 4 molecule, sCD14 and mCD14.