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

Damir Muhvic,Volker El-Samalouti,Daniel Rukavina,Hans-Dieter Flad,Biserka Radoševic-Stašic

doi:10.1080/09629350123956

Damir Muhvic, Volker El-Samalouti + Show 3 more

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https://doi.org/10.1080/09629350123956

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Abstract

Cell-wall components of Gram-positive and Gram-negative bacteria induce the production of cytokines in human peripheral blood mononuclear cells. These cytokines are the main mediators of local or systemic inflammatory reaction that can contribute to the development of innate immunity. This study was performed to analyze the involvement of CD14 molecule in the activation of human monocytes by peptidoglycan monomer (PGM) obtained by biosynthesis from culture fluid of penicillin-treated Brevibacterium divaricatum NRLL-2311. Cytokine release of interleukin (IL)-1, IL-6 and tumor necrosis factor-alpha from human monocytes via soluble CD14 (sCD14) or membrane-associated (mCD14) receptor using anti-CD14 monoclonal antibody (MEM-18) or lipid A structure (compound 406) was measured in bioassays. The results demonstrated that PGM in the presence of human serum might induce the monokine release in a dose-dependent manner. The addition of sCD14 at physiologic concentrations enhanced the PGM-induced monokine release, 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, compound 406, suggesting the involvement of binding structures similar to those for lipopolysaccharide. Activation of human monocytes by PGM involves both forms of CD14 molecule, sCD14 and mCD14.

Highlights

Cell wall components of Gram-negative and Grampositive bacteria have been reported to induce inflammatory responses in vivo, as well as in vitro.[1,2,3,4,5] When localized, this inflammation helps to eradicate the invading organisms at the infected site, but in severe situations the release of soluble cellular mediators and dysfunction of numerous host defense factors may result in systemic inflammation that causes organ damage, sepsis, and death
To prove the role of soluble CD14 (sCD14) in peptidoglycan monomer (PGM)-induced release of monokines and to compare this process with that induced by LPS, PGM or LPS were preincubated with sCD14 for 3 h and added to cultures of human monocytes in additional experiments
The concentration of IL-1 found in these cultures was compared with that found in cultures without added sCD14, with those treated with antiCD14 mAb MEM-18, and with those treated with anti-IgG1 mAb

Summary

Introduction

Cell wall components of Gram-negative and Grampositive bacteria have been reported to induce inflammatory responses in vivo, as well as in vitro.[1,2,3,4,5] When localized, this inflammation helps to eradicate the invading organisms at the infected site, but in severe situations the release of soluble cellular mediators and dysfunction of numerous host defense factors may result in systemic inflammation that causes organ damage, sepsis, and death. Septic shock is a classical response to severe infections due to Gram-negative bacteria and its principal component lipopolysaccharide (LPS).[6,7,8] Similar events, may be provoked by Gram-positive bacteria[9] containing, in cell walls, predominantly thick peptidoglycans (PG), which may be obtained in the soluble form (sPG), after the treatment of growing bacteria by b -lactam antibiotics.[10,11] Chemically, PG is an alternating linked. Cell-wall components of Gram-positive and Gram-negative bacteria induce the production of cytokines in human peripheral blood mononuclear cells. These cytokines are the main mediators of local or systemic inflammatory reaction that can contribute to the development of innate immunity. Conclusion: Activation of human monocytes by PGM involves both forms of CD14 molecule, sCD14 and mCD14

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