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After a single intraperitoneal injection of cell wall fragments of Eubacterium aerofaciens, a main resident from the human Intestinal flora, an acute arthritis develops within 2 days which is followed by a chronic arthritis that lasts at least 90 days. In an earlier report the histological appearance of the joint inflammation during this period has been described. In this study we investigated in more detail the cell types that are involved in the development of arthritis by using cell-type-specific monoclonal antibodies in an immunohistological assay. In the acute phase of arthritis. T-helper cells appeared in the synovial tissue together with ED1-positive (ED1+) and ED3-positive (ED3+) macrophages. After a temporary decline at day 12 all macrophage subsets, as well as T-helper cells, reappeared or increased again at day 33. Later, in the chronic phase (days 47-90), an increased number of ED1-positive (ED1+) cells in the synovial tissue and a decreased number of ED2-positive (ED2+) cells in the synovial lining was the most prominent finding when compared with control rats. These results indicate that, apart from T lymphocytes, macrophages also play an important role in the development and continuation of chronic arthritis in this model. [ABSTRACT FROM AUTHOR]

Previous studies have shown that polymyxin B and neomycin were bound to the solid part of human faeces. In the present study, the faecal binding of polymyxin B and neomycin was studied, using a wide range of concentrations of drugs and faecal dilutions. Up to 25 mg of polymyxin B and 15 mg of neomycin could bind to 1 g of faeces but the binding was found to be reversible. With faeces of rats it was found that polymyxin B was mainly bound to the non-bacterial part of faeces, whereas neomycin was bound to the bacterial as well as the non-bacterial part. The implications of the reversible binding of antibiotics to intestinal contents for selective decontamination are discussed. [ABSTRACT FROM PUBLISHER]

N-acetylmuramyl-L-alanine amidase (NAMLAA) specifically degrades peptidoglycan, a major component of bacterial cell walls. Lysozyme degrades peptidoglycan differently by hydrolyzing the aminosugar backbone of peptidoglycan. In another study, it was shown that the two enzymes act synergistically to inactivate the inflammatory properties of peptidoglycan. The presence of lysozyme and NAMLAA was determined in serum and cerebrospinal fluid (CSF) of patients with bacterial meningitis. High concentrations of lysozyme were found in CSF while, surprisingly, NAMLAA was not present. To explain this phenomenon, the degranulation pattern of neutrophils in CSF was compared with that of neutrophils from blood. Specific granules contain lysozyme and the azurophil granules contain both lysozyme and NAMLAA. CD66b expression on the cell surface, indicative for fusion of the specific granules with the cell membrane, was higher in CSF than in blood, while the marker for the azurophil granules was lower. [ABSTRACT FROM AUTHOR]

In previous studies using an animal model human bacterial flora-derived peptidoglycan polysaccharides were shown to be arthropathic after a single subcutaneous injection. A prerequisite for proof of the hypothesis that bacterial products from the normal resident flora are involved in the immune reaction of human chronic polyarthritis of unknown aetiology is the presence of these antigens in synovial tissue. 2E9, a monoclonal antibody we developed against intestinal peptidoglycan polysaccharides, was used in a histochemical study in rats and stained macrophages in the spleen red pulp. In this study human synovial tissues from 10 rheumatoid arthritis (RA) and 20 non-RA patients were stained with 2E9. We found that eight out of 10 RA patients had 2E9-positive macrophages and dendritic cells in their synovia. A significant difference was observed with the control group in which seven out of 20 were positive. No positive cells or staining of the matrix was found in the cartilage of six RA patients. These results show that exogenous bacterial antigens are present in synovial tissue macrophages and dendritic cells. It was concluded that the unknown antigen in the immune reaction in RA is not necessarily endogenous. [ABSTRACT FROM PUBLISHER]

Multiple sclerosis is believed to result from a CD4+ T-cell response against myelin antigens. Peptidoglycan, a major component of the Gram-positive bacterial cell wall, is a functional lipopolysaccharide analogue with potent proinflammatory properties and is conceivably a mediator of sterile inflammation. Here we demonstrate that peptidoglycan is present within antigen-presenting cells in the brain of multiple sclerosis patients. These cells have macrophage and dendritic cell characteristics, and are immunocompetent as evidenced by co-expression of inflammatory cytokines and co-stimulatory molecules. In addition, intrathecal plasma cells specific for peptidoglycan are present in multiple sclerosis brain tissue, and antibodies binding peptidoglycan are present in CSF during active disease. Peptidoglycan may thus contribute to T- and B-cell activity during brain inflammation without a requirement for local bacterial replication.

Objective: Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by intimal lining hyperplasia and massive infiltration of the synovial sublining by antigen-presenting cells (APCs), lymphocytes, and plasma cells. Peptidoglycan (PG), a major cell wall component of gram-positive bacteria, which is abundantly expressed in all mucosa, is believed to be involved in the pathogenesis of RA because of its ability to induce the production of proinflammatory cytokines as well as to induce arthritis in rodents. While PG has been detected in APCs in RA joints, little is known about the role of these cells in RA. In this study, the presence and immune competence of PG-containing cells in synovial tissues from 14 RA and 14 osteoarthritis (OA) patients were analyzed in situ., Methods: Using immunohistochemistry, we examined the coexpression of phenotypic markers, costimulatory molecules, and cytokines by PG-containing cells., Results: PG was present in higher numbers in RA than in OA synovial tissues, although the difference was not significant. PG-containing cells were mainly macrophages, but some mature dendritic cells also contained PG. A high percentage of PG-containing cells in both RA and OA synovial tissues coexpressed HLA-DR. CD40, CD80, and CD86 expression by PG-containing cells was higher in RA than in OA tissues. Furthermore, PG-containing cells coexpressed cytokines, which modulate inflammatory reactions, in particular, tumor necrosis factor alpha and interleukins 6 and 10., Conclusion: The results suggest that PG-containing cells may contribute to inflammation within the microenvironment of the joint in RA patients.

Objective: The continuous presence of bacteria or their degraded antigens in the synovium may be involved in the pathogenesis of rheumatoid arthritis (RA). The aim of this study was to determine the presence of bacterial nucleic acids and bacterial cell wall constituents in the joints of patients with RA and other forms of arthritis., Methods: Joint samples were obtained from patients with RA (n = 26), septic arthritis (n = 2), inflammatory osteoarthritis (n = 5), and gout (n = 6), and joint trauma (n = 1). Universal 16S-ribosomal RNA primers were used to detect the presence of bacterial DNA in these samples, using stringent regimens for sample collection and molecular microbiologic analysis. Automated sequencing and comparative data analysis were performed to identify the species. The presence of bacterial peptidoglycan-polysaccharide complexes in synovial tissue was detected by immunohistologic analysis with a specific antibody., Results: The bacterial species cultured from the synovium could be identified in both of the patients with septic arthritis. DNA amplicons were also detected in the synovial fluid and/or tissue samples from 5 patients with RA and 2 patients with crystal-induced arthritis; these originated from multiple bacterial species. Staining for peptidoglycan-polysaccharide complexes was positive in the synovial tissue of both patients with septic arthritis, 16 with RA, 4 with inflammatory osteoarthritis, 4 with crystal-induced arthropathy, and 1 with joint trauma. The staining was mainly found in cells in the synovial sublining, including macrophages., Conclusion: The results indicate that bacterial DNA and bacterial cell wall constituents are retained in the joints of some patients with arthritis, where they might enhance synovial inflammation.