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

BACKGROUND: 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. AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Activation of human monocytes by PGM involves both forms of CD14 molecule, sCD14 and mCD14

Importance of immunological and inflammatory processes in the pathogenesis and therapy of Alzheimer's disease

The contribution of autoimmune processes or inflammatory components in the etiology and pathogenesis of Alzheimer's disease (AD) has been suspected for many years. The presence of antigen-presenting, HLA-DR-positive and other immunoregulatory cells, components of complement, inflammatory cytokines and acute phase reactants have been established in tissue of AD neuropathology. Although these data do not confirm the immune response as a primary cause of AD, they indicate involvement of immune processes at least as a secondary or tertiary reaction to the preexisting pathogen and point out its driving-force role in AD pathogenesis. These processes may contribute to systemic immune response. Thus, experimental and clinical studies indicate impairments in both humoral and cellular immunity in an animal model of AD as well as in AD patients. On the other hand, anti-inflammatory drugs applied for the treatment of some chronic inflammatory diseases have been shown to reduce risk of AD in these patients. Therefore, it seems that anti-inflammatory drugs and other substances which can control the activity of immunocompetent cells and the level of endogenous immune response can be valuable in the treatment of AD patients