Synovial Fluid Muramic Acid in Acute Inflammatory Arthritis

Lehtonen, L.; Kortekangas, P.; Oksman, Pentti; Eerola, Erkki; Aro, Hannu T.; Toivanen, Auli

doi:10.1093/rheumatology/33.12.1127

Cited by 29 publications

(23 citation statements)

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“…Regarding the pathogenesis of human rheumatoid arthritis, it should be emphasized that (i) the E. aerofaciens strains used here originate in the normal gut flora of humans, (ii) degradation products derived from the normal gut flora are present in the circulation of healthy individuals (21,22), and (iii) bacterial CW debris has been demonstrated in the synovial tissues of patients with inflammatory arthritis (23,26,29,34,47). Therefore, the bacterial composition of the individual intestinal flora might represent a crucial factor contributing to the potential role of intestinal bacteria in the pathogenesis of rheumatoid arthritis.…”

Section: Vol 69 2001mentioning

confidence: 99%

Enzyme Degradation and Proinflammatory Activity in Arthritogenic and NonarthritogenicEubacterium aerofaciensCell Walls

et al. 2001

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Two almost-identical strains of Eubacterium aerofaciens isolated from the normal human gut flora were used. The cell wall (CW) of one strain with a peptidoglycan (PG) type A4␣ induces chronic arthritis in the rat after a single intraperitoneal injection, whereas CW of the other with PG type A4␤ induces only a transient acute arthritis. The CW of the arthritogenic E. aerofaciens was a twofold-more-potent stimulator of the proinflammatory cytokines tumor necrosis factor alpha (TNF-␣) and monocyte chemoattractant protein 1 (MCP-1) than the nonarthritogenic CW. After degradation with mutanolysin, the capacity of the arthritogenic PG to stimulate production of TNF-␣ and MCP-1 was significantly increased, whereas that of the nonarthritogenic PG was significantly decreased. In other words, after enzyme degradation the arthritogenic PG had a four-to fivefoldstronger stimulatory capacity than that of the enzyme-treated nonarthritogenic PG. These findings indicate that the arthritogenicity of CW or a PG is not dependent on the enzyme resistance alone but also on how the PG fragments released by enzyme degradation stimulate the production of proinflammatory cytokines.Bacterial cell wall (CW) arthritis induced by a single intraperitoneal (i.p.) injection of gram-positive CWs in the rats is an experimental model closely resembling human rheumatoid arthritis. Using this model, we have described two bacterial strains of the same species, Eubacterium aerofaciens, one with a CW causing chronic arthritis and another with a CW causing only a transient acute arthritis. Both strains were isolated as a part of the normal human intestinal flora. They are 100% identical by the 16S ribosomal DNA (rDNA) analysis and have slightly different cellular fatty acid and biochemical profiles, indicating that they are clones of the same species (53). Chronic arthritis can be induced by using peptidoglycan (PG)-polysaccharide polymers isolated from the CW. The significance of polysaccharides seems to be to protect PG from enzyme degradation (4, 10, 35, 52), and for the induction of chronic arthritis the chemical structure of the PG moiety is decisive (52). The E. aerofaciens CW causing chronic arthritis has a PG of type A4␣, and the CW of the strain causing only a mild, transient arthritis has a PG of type A4␤. These two strains of E. aerofaciens have been designated arthritogenic and nonarthritogenic strains, respectively (53).PG in gram-positive CWs consists of several layers (up to 70) of sugar chains containing N-acetylmuramic acid (MurNAc) and N-acetylglucosamine (GlcNAc) alternatively linked to each other by ␤-1,4-glycosidic bonds (Fig. 1). Stem peptides, also called muramyl peptides, are short peptides of four to five amino acids bound to MurNAc. PG and muramyl peptides possess multiple immune activities (3,17,24,25,42). For instance, PG can bind to CD14 (6) and to Toll-like receptor 2 (36, 51) to stimulate T cells and monocytes to produce inflammatory cytokines, including tumor necrosis factor alpha (TNF-␣), interleukin (IL-8), and monocyt...

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Section: Vol 69 2001mentioning

confidence: 99%

Enzyme Degradation and Proinflammatory Activity in Arthritogenic and NonarthritogenicEubacterium aerofaciensCell Walls

et al. 2001

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“…(Adaptiert nach [1 [12][13][14][15][16][17][18]. Eine synoviale Lymphozytenproliferation als Immunantwort und spezifische DNA Analysen mittels PCR können hingegen wichtige Hinweise auf das Vorliegen einer infektiösen/ reaktiven Arthritis geben [19][20][21][22][23][24][25][26][27][28][29][30].…”

Section: Fragestellungunclassified

Evidenzbasierte Empfehlungen zum Management einer undifferenzierten peripheren entzündlichen Arthritis (UPIA)

et al. 2014

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Arthritiden der peripheren Gelenke stellen einen der häufigsten Gründe für eine Vorstellung beim Rheumatologen dar. Allerdings gelingt im klinischen Alltag bei einer großen Anzahl von Patienten mit Arthritis der peripheren Gelenke keine eindeutige differenzialdiagnostische Zuordnung zu einer definierten Entität. Dies ist insbesondere, wenn auch nicht ausschließlich, in frühen Erkrankungsstadien der Fall. In dieser Situation wird das Krankheitsbild zunächst als undifferenzierte periphere entzündliche Arthritis (UPIA) bezeichnet.

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“…It has also been reported that Mur is detectable in reactive arthritis. However, in the majority of cases, the levels are so low that detection proves elusive (27). These studies demonstrate the utility of nontraditional, gas chromatography-mass spectrometry (GC-MS) and more advanced GC-MS 2 techniques in demonstrating the presence of bacteria in human body fluids.…”

mentioning

confidence: 90%

“…Mur is readily demonstrated in body fluids in documented infection, including septic arthritis (7,14,27), bacterial meningitis (23), and urinary tract infections (2). It has also been reported that Mur is detectable in reactive arthritis.…”

mentioning

confidence: 98%

Muramic Acid Is Not Generally Present in the Human Spleen as Determined by Gas Chromatography-Tandem Mass Spectrometry

2002

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It has been hypothesized that bacterial debris may accumulate in tissues of the reticuloendothelial system (RES) serving as an inflammatory stimulus for human disease. In support of this hypothesis, muramic acid (Mur), a component of bacterial peptidoglycan (PG), has previously been reported to be present in culturenegative human spleen. High-performance liquid chromatography (HPLC) was employed in these analyses, and a peak was detected at the retention time of Mur. However, HPLC is best used as a screening technique, and it is vital that these tentative observations be reexamined by the state-of-the-art approach (gas chromatography-tandem mass spectrometry [GC-MS 2 ]). Indeed, in the present work using GC-MS 2 , Mur was not detected in six out of seven human spleens previously examined by HPLC. However, Mur was categorically detected at minute concentrations, 50 ppb, in one spleen. In conclusion, since Mur is not generally found in culture-negative human spleen, in future studies, these tissues can serve as negative controls. The study of Mur levels in inflammation (e.g., reactive arthritis) could prove important in testing the hypothesis that bacterial debris persisting in tissues could serve as a depot inciting diseases of unknown etiology.

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Synovial Fluid Muramic Acid in Acute Inflammatory Arthritis

Cited by 29 publications

References 0 publications

Enzyme Degradation and Proinflammatory Activity in Arthritogenic and NonarthritogenicEubacterium aerofaciensCell Walls

Enzyme Degradation and Proinflammatory Activity in Arthritogenic and NonarthritogenicEubacterium aerofaciensCell Walls

Evidenzbasierte Empfehlungen zum Management einer undifferenzierten peripheren entzündlichen Arthritis (UPIA)

Muramic Acid Is Not Generally Present in the Human Spleen as Determined by Gas Chromatography-Tandem Mass Spectrometry

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