A 48-kilodalton Mycoplasma fermentans membrane protein induces cytokine secretion by human monocytes

Kostyal, David; Butler, Gary H.; Beezhold, Donald H.

doi:10.1128/iai.62.9.3793-3800.1994

Cited by 45 publications

(32 citation statements)

References 37 publications

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“…Our results are in line with several recent publications reporting the upregulation of TNF-␣, IL-1␤, and IL-6 expression after stimulation of monocytes with mycoplasma-derived membrane fractions (16,22,25). Gamma interferon pretreatment of murine peritoneal macrophages was reported to induce large amounts of nitric oxide when the cells were subsequently stimulated with a mycoplasma-derived high-molecular-weightmaterial (MDHM) (22).…”

Section: Discussionsupporting

confidence: 92%

“…Also, infections with cell wall-free mycoplasmas may be associated with strong inflammatory reactions. Recently, some reports demonstrated the macrophage-stimulatory activity of mycoplasmas or mycoplasmaderived lipoprotein fractions in vitro (9,16,26), suggesting that mycoplasma lipoproteins may be directly responsible for the induction of cytokines and chemokines. In this study, we used MALP-2, a chemically well defined prototype of a mycoplasma-derived lipopeptide, and investigated in detail the spectrum of inflammatory mediators that were released in response to this compound.…”

Section: Discussionmentioning

confidence: 99%

“…However, also preparations from mycoplasmas can powerfully stimulate macrophages/monocytes (2,6,15,33,34), although these microorganisms lack a cell wall. Recently, several reports demonstrated that crude fractions of lipoproteins derived from different mycoplasma strains showed macrophage-stimulatory activities by inducing the production of proinflammatory cytokines (9,16,26). In a more detailed analysis, the lipopeptide MALP-2 (macrophage-activating lipopeptide 2), recently isolated from a clone of Mycoplasma fermentans, has been shown to induce proinflammatory cytokines as well as nitric oxide release from mouse peritoneal macrophages (23).…”

mentioning

confidence: 99%

“…In a more detailed analysis, the lipopeptide MALP-2 (macrophage-activating lipopeptide 2), recently isolated from a clone of Mycoplasma fermentans, has been shown to induce proinflammatory cytokines as well as nitric oxide release from mouse peritoneal macrophages (23). The structure was determined to be S- [2,3-bisacyloxypropyl]cysteine-GNNDESNISFKEK, with 1 mol of C 16:0 and a further mol of a mixture of C 18:0 and C 18:1 fatty acid per lipopeptide molecule (23). MALP-2 is probably derived from the larger lipoprotein MALP-404 by posttranslational cleavage (33).…”

mentioning

confidence: 99%

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Induction of Cytokines and Chemokines in Human Monocytes byMycoplasma fermentans-Derived Lipoprotein MALP-2

et al. 1999

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Bacterial infections are characterized by strong inflammatory reactions. The responsible mediators are often bacterially derived cell wall molecules, such as lipopolysaccharide or lipoteichoic acids, which typically stimulate monocytes and macrophages to release a wide variety of inflammatory cytokines and chemokines. Mycoplasmas, which lack a cell wall, may also stimulate monocytes very efficiently. This study was performed to identify mycoplasma-induced mediators. We investigated the induction of cytokines and chemokines in human monocytes exposed to the Mycoplasma fermentans-derived membrane component MALP-2 (macrophage-activating lipopeptide 2) by dose response and kinetic analysis. We found a rapid and strong MALP-2-inducible chemokine and cytokine gene expression which was followed by the release of chemokines and cytokines with peak levels after 12 to 20 h. MALP-2 induced the neutrophil-attracting CXC chemokines interleukin-8 (IL-8) and GRO-␣ as well as the mononuclear leukocyte-attracting CC chemokines MCP-1, MIP-1␣, and MIP-1␤. Production of the proinflammatory cytokines tumor necrosis factor alpha and IL-6 started at the same time as chemokine release but required 10-to 100-fold-higher MALP-2 doses. The data show that the mycoplasma-derived lipopeptide MALP-2 represents a potent inducer of chemokines and cytokines which may, by the attraction and activation of neutrophils and mononuclear leukocytes, significantly contribute to the inflammatory response during mycoplasma infection.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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confidence: 99%

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Induction of Cytokines and Chemokines in Human Monocytes byMycoplasma fermentans-Derived Lipoprotein MALP-2

et al. 1999

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“…As another interesting finding, we have shown that IgG antibodies present in SF of our patients have a high affinity to certain M. fermentans membrane lipoproteins, including p48 and p29. p48 was recently shown to be an arthritogenic antigen to induce TNFproduction from human monocytes 31 . More interestingly, various Mycoplasma species were shown to have affinity to cartilage, possibly promoting the homing of the bacteria to the joint tissue 32 .…”

Section: Differences In the Specificity To Certain Lipoproteins Detecmentioning

confidence: 99%

Detection of DNA and Immunoreactivity Specific for Mycoplasma fermentans in Synovial Fluid and Sera from Patients with Temporomandibular Joint Disorders

Suga

Kubota

Shibata

2004

Oral Science International

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This study investigated whether the presence of Mycoplasma fermentans (M. fermentans) in the temporomandibular joint (TMJ) could be associated with the pathology of temporomandibular joint disorders (TMD). One hundred fifteen synovial fluid (SF) samples from patients with TMD were evaluated for the presence of DNA of M. fermentans by polymerase chain reaction (PCR) assay. Specific antibody against M. fermentans was also detected in the SF as well as sera by Western blot analysis. M. fermentans DNA was identified in 37.4％ of the SF samples from the TMD patients. There was no difference between PCR‐positive and ‐negative rate regarding sex and disease categories, e.g., internal derangement (ID) and osteoarthritis (OA). However, the prevalence of M. fermentans DNA in ID patients was higher in elderly patients (73.3％) than in younger patients(31.8％). Anti‐M. fermentans immunoreactivities (IgG) specific for lipoproteins with various molecular sizes, 56 kilo‐Dalton (kDa), 48 kDa, 38 kDa, and 29 kDa, were also identified in the SF. The immunoreactivity was also detected in the patients’ sera. The reactivity patterns of the anti‐M. fermentans antibodies were, however, different between the SF and the sera ; reactivities to 48 kDa and 29 kDa lipoproteins were prominent in the former, while the reactivities to those of 56 kDa, 48 kDa, and 29 kDa were evidently increased in the latter. The presence of specific DNA and antibody for M. fermentans in the TMJ implies that M. fermentans could possibly induce joint specific immunoreaction, thus perpetuating the inflammatory reaction in the diseased TMJ.

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Mycoplasma fermentans‐derived lipid inhibits class II major histocompatibility complex expression without mediation by interleukin‐6, interleukin‐10, tumor necrosis factor, transforming growth factor‐β, type I interferon, prostaglandins or nitric oxide

1996

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Mycoplasma cause several diseases in man and animals. Some strains can chronically infect humans, leading to fever or inflammatory syndromes such as arthritis, particularly in immunosuppressed patients. A set of pathogenicity factors shared by many mollicutes may be membrane components that activate macrophages to secrete cytokines and other inflammatory mediators. Mycoplasma-derived high molecular weight material (MDHM) is a macrophage-activating amphiphilic lipid which was purified from Mycoplasma fermentans. We studied the influence of MDHM on the expression of major histocompatibility complex (MHC) class II molecules by mouse resident peritoneal macrophages with an ELISA. Highly purified MDHM at 4 ng/ml and 0.8 microgram/ml crude heat-killed M. fermentans (concentrations chosen to give maximal responses) suppressed interferon (IFN)-gamma-dependent class II MHC induction when added simultaneously with IFN-gamma. MDHM was not toxic and did not result in loss of adherent cells. Kinetic data showed that MDHM first up-regulated, then down-regulated the expression of preformed class II MHC molecules, while expression of Mac-1 and F4/80 antigens remained constant. MDHM-dependent suppression of class II MHC molecule expression resulted in impaired antigen presentation to the helper T cell line D10.G4.1. We further attempted to identify hypothetical products of MDHM-stimulated macrophages as secondary mediators of class II MHC suppression such as were described for lipopolysaccharide (LPS)-stimulated macrophages. Type I IFN, prostaglandins and nitric oxide, all reported to cause down-regulation of class II MHC, could be excluded in this context. Of the cytokines tumor necrosis factor, interleukin (IL)-6, IL-10 and transforming growth factor-beta, only IL-10 inhibited class II MHC expression, although less effectively than MDHM. The involvement of IL-10 was ruled out, as no evidence for its MDHM-dependent formation could be found. Our data suggest that MDHM interferes with class II MHC expression by up-regulating its turnover, and at the same time, inhibits the formation of new class II MHC molecules.

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A 48-kilodalton Mycoplasma fermentans membrane protein induces cytokine secretion by human monocytes

Cited by 45 publications

References 37 publications

Induction of Cytokines and Chemokines in Human Monocytes byMycoplasma fermentans-Derived Lipoprotein MALP-2

Induction of Cytokines and Chemokines in Human Monocytes byMycoplasma fermentans-Derived Lipoprotein MALP-2

Detection of DNA and Immunoreactivity Specific for Mycoplasma fermentans in Synovial Fluid and Sera from Patients with Temporomandibular Joint Disorders

Mycoplasma fermentans‐derived lipid inhibits class II major histocompatibility complex expression without mediation by interleukin‐6, interleukin‐10, tumor necrosis factor, transforming growth factor‐β, type I interferon, prostaglandins or nitric oxide

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