Muramic acid in human peripheral blood leucocytes in different age groups

Lehtonen, L.; Eerola, Erkki; Toivanen, Paavo

doi:10.1046/j.1365-2362.1997.1950732.x

Cited by 13 publications

(8 citation statements)

References 9 publications

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“…Interestingly, PG retaining proinflammatory capacity such as the induction of TNF-α and IL-1, can be fractionated from sterile human spleen (Timmerman et al, 1993;Weidemann et al, 1994;Schrijver et al, 1999), suggesting that continuous redistribution of PG occurs from the mucosa to the secondary lymphoid organs, as well as to other anatomical sites in the absence of sepsis, and without requirement for local bacterial replication. This is fully consistent with the presence of circulating leucocytes carrying PG in human healthy subjects (Lehtonen et al, 1995) and distinct patient categories (Lehtonen et al, 1997).…”

Section: © Oxford University Press 2001supporting

confidence: 87%

Bacterial peptidoglycan and immune reactivity in the central nervous system in multiple sclerosis

Schrijver¹,

Meurs²,

Melief³

et al. 2001

Brain

116

100

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SummaryMultiple sclerosis is believed to result from a CD4ϩ 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,

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Section: © Oxford University Press 2001supporting

confidence: 87%

Bacterial peptidoglycan and immune reactivity in the central nervous system in multiple sclerosis

Schrijver¹,

Meurs²,

Melief³

et al. 2001

Brain

116

100

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“…The presence of PG, an antigen that is ubiquitously available at mucosal sites, in synovial tissues suggests that PG is transported by monocytes that are circulating through the bloodstream (23,24) and can enter the synovial tissue. The redistribution of PG to nonmucosal sites may be dependent on 3 factors.…”

Section: Discussionmentioning

confidence: 99%

“…PG isolated from the anaerobic bacterium Eubacterium aerofaciens, which is present in numbers Ͼ10 9 /gm of human feces, induces a severe and chronic arthritis in rats (20). The presence of PG in healthy human tissues, such as the spleen (21), lymph nodes, liver (22), and blood cells (23,24), indicates that PG may circulate through the body without producing any signs of bacterial infection. That PG present in human tissues is still biologically active has been shown after the in vitro analysis of PG isolated from human spleen.…”

Section: Containing Cells May Contribute To Inflammation Within the Mmentioning

confidence: 99%

Antigen-presenting cells containing bacterial peptidoglycan in synovial tissues of rheumatoid arthritis patients coexpress costimulatory molecules and cytokines

Schrijver

Melief

Tak

et al. 2000

Arthritis & Rheumatism

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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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Muramic acid in human peripheral blood leucocytes in different age groups

Cited by 13 publications

References 9 publications

Bacterial peptidoglycan and immune reactivity in the central nervous system in multiple sclerosis

Bacterial peptidoglycan and immune reactivity in the central nervous system in multiple sclerosis

Antigen-presenting cells containing bacterial peptidoglycan in synovial tissues of rheumatoid arthritis patients coexpress costimulatory molecules and cytokines

Enzyme Degradation and Proinflammatory Activity in Arthritogenic and NonarthritogenicEubacterium aerofaciensCell Walls

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