engleski

Peptidoglycan monomer induces cytokine production in human mononuclear cells via CD14

Peptidoglycan (PG) and lipopolisaccharide (LPS) are the major components of the cell walls of gram-positive and gram-negative bacteria, respectively. Both are biologically active substances which can reproduce most of the clinical manifestations of bacterial infections. Because of the similarity of the biological effects of peptidoglycan and lipopolysaccharide (LPS) we decided to test the hypothesis that CD14 is the receptor not only for LPS but also for peptidoglycan monomer (PGM). PGM was isolated by enzymic cutting of soluble peptidoglycanic polymers obtained from gram-positive bacteria Brevibacterium divaricatum and has disaccharide-pentapeptide structure. The biological activity of two peptidoglycan monomers, peptidoglycan monomer (PGM) and peptidoglycan monomer linked with zinc (PGM-Zn) was tested by measuring the cytokine production of interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor (TNF) in human mononuclear cells (MNC) isolated from peripheral blood of a healty donors. The results have shown that similarly to LPS, PGM and PGM-Zn are able to induce the production of IL1, IL6 and TNF in human MNC only in the presence of 10% human heterologous serum (HHS). PGM and LPS were also able to induce TNF production in human MNC in the presence of 10% HHS. This activity was blocked by anti-CD14 monoclonal antibody MEM-18 and by syntetic partial structure of LPS such as compound 406 (precursor Ia). Soluble human recombinant CD14 showed very potent increasing capacity on PGM-induced and LPS-induced IL-1 production in the human MNC even in the absence of 10% HHS. These is the first evidence that PGM and PGM-Zn, as peptidoglycan monomers, are able to induce cytokine production in human MNC also like peptidoglycan polymers (B.Weidemann et al., Infect. Immun., 62:, 4709, 1994). These results also for the first time show that cytokine production in human MNC induced by PGM is CD14 dependent and that soluble human recombinant CD14 is important serum factor which can augment the PGM activity. These data are indicating that CD14 can act as a receptor not only for LPS but also for PGM.

peptidoglycan monomer; CD14; cytokine production; human peripheral blood mononuclear cells

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