Mycoplasma cells stimulate in vitro activation of plasminogen by purified tissue-type plasminogen activator

Tarshis, Mark; Morag, Bilha; Mayer, Michael

doi:10.1111/j.1574-6968.1993.tb05959.x

Cited by 9 publications

(3 citation statements)

References 21 publications

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“…In the absence of cells, activation of Pg was significantly lower, reaching, after 45 min of incubation, about 60% of the activation levels observed in the presence of mycoplasmas, suggesting that the interaction of Pg or tcuPA with the cells facilitates the formation of active plasmin. The effect of M. fermentans cells on tcuPA activation was less pronounced than the effect of these cells on tPA (tissue Pg activator) enhanced activity of Pg (30). The figure also shows that no hydrolysis of S-2251 was observed in a medium containing M. fermentans cells and Pg, but without tcuPA, suggesting that M. fermentans does not produce plasmin activators such as streptokinase and staphylokinase (19).…”

Section: Resultsmentioning

confidence: 52%

Plasminogen Binding and Activation by Mycoplasma fermentans

Yavlovich¹,

Higazi

Rottem³

2001

Infect Immun

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The binding of plasminogen to Mycoplasma fermentans was studied by an immunoblot analysis and by a binding assay using iodine-labeled plasminogen. The binding of 125 I-labeled plasminogen was inhibited by unlabeled plasminogen, lysine, and lysine analog -aminocaproic acid. Partial inhibition was obtained by a plasminogen fragment containing kringles 1 to 3 whereas almost no inhibition was observed with a fragment containing kringle 4. Scatchard analysis revealed a dual-phase interaction, one with a dissociation constant Mycoplasmas (class Mollicutes) are wall-less prokaryotes widely distributed in nature. Most mycoplasmas are parasites, exhibiting strict host and tissue specificities, and almost all of them are bound to the surface of the host cell (22, 24). Human pathogen Mycoplasma fermentans was isolated from the urogenital tract several decades ago (25). The interest in this organism has recently increased because of its possible role in the pathogenesis of rheumatoid arthritis and reports indicating that this organism may function as a cofactor accelerating the progression of human immunodeficiency virus disease (17, 23).Plasminogen (Pg) is a 92-kDa plasma glycoprotein. This protein is activated in vivo to the serine protease plasmin by urokinase-type and tissue-type Pg activators (uPA and tPA, respectively) by cleavage of a single peptide bond (R 561 -V 562 ) yielding two chains that remain connected by two disulfide bridges (26). Plasmin participates in several physiological and pathophysiological processes such as fibrinolysis, pericellular proteolysis, tissue penetration of cancer cells, and neuronal cell death (19,21,26). The active domain of Pg is located in the COOH terminal of the molecule, whereas the NH 2 terminal contains five characteristic triple-loop structures (kringles) that mediate the interaction of Pg with a variety of ligands such as fibrin, the ␣ 2 -plasmin inhibitor, etc. (21). This interaction is between lysine-binding sites in the kringles and exposed COOH-terminal lysines in the ligands (26). Therefore, lysine or lysine analogs such as ε-aminocaproic acid (εACA) mimic COOH-terminal lysine by inhibiting the interaction.Many eucaryotic cells express surface structures that interact with Pg, and specific receptors have been described (21). Recently it became evident that Pg is also capable of interacting with receptors on several prokaryotic organisms, including both gram-positive (4, 15, 18, 34) and gram-negative bacteria (12,13,20,32,33). In the present study we extend the group of bacteria capable of binding Pg to include the wall-less M. fermentans and show that Pg interacts with two surface proteins of this organism. The association of Pg with M. fermentans greatly enhances its uPA-associated activation. The possible role of Pg binding in M. fermentans-host interactions is discussed. MATERIALS AND METHODSOrganisms and growth conditions. M. fermentans strain PG-18 was used throughout the study. In some experiments strains M-52, M-32, AOU, and Z-62 (kindly provided by P. Hannan, Sur...

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Section: Resultsmentioning

confidence: 52%

Plasminogen Binding and Activation by Mycoplasma fermentans

Yavlovich¹,

Higazi

Rottem³

2001

Infect Immun

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“…We did not test delayed application of tPA, but the addition of plasminogen plus a very small amount of tPA resulted in the same degree of neuronal killing resulting from OGD, suggesting a lack of plasminogen substrate. It is also possible that the culture medium contained an inhibitor of lysine-binding sites on either tPA or plasminogen, which would elevate the threshold for plasminogen activation (Tarshis et al, 1993). As always, comparison of in vivo and in vitro findings can be misleading.…”

Section: Discussionmentioning

confidence: 99%

Tissue plasminogen activator protects hippocampal neurons from oxygen-glucose deprivation injury

Flavin

Zhao

2001

J. Neurosci. Res.

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“…Since both SARS-CoV-2 and Mycoplasma species bind FBN and express the RGD motif, they may fuse with each other, engendering a combined pathology [206,209,210]. In addition, it has been established that Mycoplasma fermentans incognitus strain stimulates tissue plasminogen activator (tPA) which converts plasminogen to plasmin, a protein that, like furin, can cleave the SARS-CoV-2 S antigen at the S1/S2 site, triggering pathological cell-cell fusion [211][212][213]. Elevated plasmin and plasminogen levels are common findings in severe COVID-19 illness as well as in patients with various chronic diseases, including hypertension, diabetes, and cardiovascular diseases.…”

Section: Rethinking Mycoplasmamentioning

confidence: 99%

Long COVID and the Neuroendocrinology of Microbial Translocation Outside the GI Tract: Some Treatment Strategies

Sfera

Osorio

Hazan³

et al. 2022

Endocrines

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Similar to previous pandemics, COVID-19 has been succeeded by well-documented post-infectious sequelae, including chronic fatigue, cough, shortness of breath, myalgia, and concentration difficulties, which may last 5 to 12 weeks or longer after the acute phase of illness. Both the psychological stress of SARS-CoV-2 infection and being diagnosed with COVID-19 can upregulate cortisol, a stress hormone that disrupts the efferocytosis effectors, macrophages, and natural killer cells, leading to the excessive accumulation of senescent cells and disruption of biological barriers. This has been well-established in cancer patients who often experience unrelenting fatigue as well as gut and blood–brain barrier dysfunction upon treatment with senescence-inducing radiation or chemotherapy. In our previous research from 2020 and 2021, we linked COVID-19 to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) via angiotensin II upregulation, premature endothelial senescence, intestinal barrier dysfunction, and microbial translocation from the gastrointestinal tract into the systemic circulation. In 2021 and 2022, these hypotheses were validated and SARS-CoV-2-induced cellular senescence as well as microbial translocation were documented in both acute SARS-CoV-2 infection, long COVID, and ME/CFS, connecting intestinal barrier dysfunction to disabling fatigue and specific infectious events. The purpose of this narrative review is to summarize what is currently known about host immune responses to translocated gut microbes and how these responses relate to fatiguing illnesses, including long COVID. To accomplish this goal, we examine the role of intestinal and blood–brain barriers in long COVID and other illnesses typified by chronic fatigue, with a special emphasis on commensal microbes functioning as viral reservoirs. Furthermore, we discuss the role of SARS-CoV-2/Mycoplasma coinfection in dysfunctional efferocytosis, emphasizing some potential novel treatment strategies, including the use of senotherapeutic drugs, HMGB1 inhibitors, Toll-like receptor 4 (TLR4) blockers, and membrane lipid replacement.

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Mycoplasma cells stimulate in vitro activation of plasminogen by purified tissue-type plasminogen activator

Cited by 9 publications

References 21 publications

Plasminogen Binding and Activation by Mycoplasma fermentans

Plasminogen Binding and Activation by Mycoplasma fermentans

Tissue plasminogen activator protects hippocampal neurons from oxygen-glucose deprivation injury

Long COVID and the Neuroendocrinology of Microbial Translocation Outside the GI Tract: Some Treatment Strategies

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