Plasmin activity in the porcine airways is enhanced during experimental infection with Mycoplasma hyopneumoniae, is positively correlated with proinflammatory cytokine levels and is ameliorated by vaccination

Woolley, Lauren K.; Fell, Shayne A.; Djordjevic, Steven P.; Eamens, G. J.; Jenkins, Cheryl

doi:10.1016/j.vetmic.2013.02.003

Cited by 24 publications

(23 citation statements)

References 33 publications

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“…Significant increase in both plasminogen and cleaved plasmin protein in the BAL of ARDS patients (32) and an animal model of DAD (33) have been reported. Augmented plasmin activity contributes to elevated D-dimer in the BAL of infected lungs in a timedependent manner during the development of ARDS (20,87). This is further validated by the observation that plasmin-mediated fibrinolytic activity could be inhibited by 50% with ␣2-antiplasmin antibody (32).…”

Section: A Plasmin(ogen) Is Increased In Ardsmentioning

confidence: 71%

Elevated Plasmin(ogen) as a Common Risk Factor for COVID-19 Susceptibility

Zhao

Matalon

et al. 2020

Physiological Reviews

354

379

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Patients with hypertension, diabetes, coronary heart disease, cerebrovascular illness, chronic obstructive pulmonary disease, and kidney dysfunction have worse clinical outcomes when infected with SARS-CoV-2, for unknown reasons. The purpose of this review is to summarize the evidence for the existence of elevated plasmin(ogen) in COVID-19 patients with these comorbid conditions. Plasmin, and other proteases, may cleave a newly inserted furin site in the S protein of SARS-CoV-2, extracellularly, which increases its infectivity and virulence. Hyperfibrinolysis associated with plasmin leads to elevated D-dimer in severe patients. The plasmin(ogen) system may prove a promising therapeutic target for combating COVID-19.

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Section: A Plasmin(ogen) Is Increased In Ardsmentioning

confidence: 71%

Elevated Plasmin(ogen) as a Common Risk Factor for COVID-19 Susceptibility

Zhao

Matalon

et al. 2020

Physiological Reviews

354

379

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“…M. hyopneumoniae promotes the conversion of plasminogen to plasmin in the bronchoalveolar lavage fluid (BALF) bathing the respiratory tract of pigs. This is evidenced by elevated levels of plasmin in the BALF of pigs infected with M. hyopneumoniae when compared with BALF recovered from identical animals prior to experimental challenge (Seymour et al ., ; Woolley et al ., ) and by the significant correlation between bacterial load and plasmin activity in the BALF of experimentally challenged pigs (Woolley et al ., ). Plasmin levels also correlate significantly with the levels of pro‐inflammatory cytokines TNF‐α, IL‐1β and IL‐6 in the BALF at 21 days post‐challenge with M. hyopneumoniae (Woolley et al ., ).…”

Section: Discussionmentioning

confidence: 99%

Proteolytic processing of the cilium adhesin MHJ_0194 (P123_J) inMycoplasma hyopneumoniaegenerates a functionally diverse array of cleavage fragments that bind multiple host molecules

et al. 2014

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SummaryMycoplasma hyopneumoniae, the aetiological agent of porcine enzootic pneumonia, regulates the presentation of proteins on its cell surface via endoproteolysis, including those of the cilial adhesin P123 (MHJ_0194). These proteolytic cleavage events create functional adhesins that bind to proteoglycans and glycoproteins on the surface of ciliated and non-ciliated epithelial cells and to the circulatory host molecule plasminogen. Two dominant cleavage events of the P123 preprotein have been previously characterized; however, immunoblotting studies suggest that more complex processing events occur. These extensive processing events are characterized here. The functional significance of the P97 cleavage fragments is also poorly understood. Affinity chromatography using heparin, fibronectin and plasminogen as bait and peptide arrays were used to expand our knowledge of the adhesive capabilities of P123 cleavage fragments and characterize a novel binding motif in the C-terminus of P123. Further, we use immunohistochemistry to examine in vivo, the biological significance of interactions between M. hyopneumoniae and fibronectin and show that M. hyopneumoniae induces fibronectin deposition at the site of infection on the ciliated epithelium. Our data supports the hypothesis that M. hyopneumoniae possesses the molecular machinery to influence key molecular communication pathways in host cells.

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“…At the same time, M. hyopneumoniae modulates the immune response to persist in the host. Pro‐inflammatory cytokines such as IL‐1, TNF‐α and IL‐6 are induced during infection, and plasmin is recognized as central to the regulation of inflammatory responses (Woolley, Fell, Djordjevic, Eamens, & Jenkins, ). A number of the P97/P102 adhesin family members interact with plasminogen of the porcine host and enhance its activation to plasmin, a serine protease which in turn stimulates macrophage signalling resulting in production of ROS and cytokine release, thereby contributing to inflammation (Syrovets, Lunov, & Simmet, ).…”

Section: Pathogenicitymentioning

confidence: 99%

“…At the same time, M. hyopneumoniae modulates the immune response to persist in the host. Pro-inflammatory cytokines such as IL-1, TNF-a and IL-6 are induced during infection, and plasmin is recognized as central to the regulation of inflammatory responses (Woolley, Fell, Djordjevic, Eamens, & Jenkins, 2013).…”

Section: Comparative Studies With Other Mycoplasmasmentioning

confidence: 99%

Update onMycoplasma hyopneumoniaeinfections in pigs: Knowledge gaps for improved disease control

Maes

Sibila

Kuhnert

et al. 2017

Transbound Emerg Dis

207

229

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SummaryMycoplasma hyopneumoniae (M. hyopneumoniae) is the primary pathogen of enzootic pneumonia, a chronic respiratory disease in pigs. Infections occur worldwide and cause major economic losses to the pig industry. The present paper reviews the current knowledge on M. hyopneumoniae infections, with emphasis on identification and analysis of knowledge gaps for optimizing control of the disease. Close contact between infected and susceptible pigs is the main route of M. hyopneumoniae transmission. Management and housing conditions predisposing for infection or disease are known, but further research is needed to better understand M. hyopneumoniae transmission patterns in modern pig production systems, and to assess the impor-

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Plasmin activity in the porcine airways is enhanced during experimental infection with Mycoplasma hyopneumoniae, is positively correlated with proinflammatory cytokine levels and is ameliorated by vaccination

Cited by 24 publications

References 33 publications

Elevated Plasmin(ogen) as a Common Risk Factor for COVID-19 Susceptibility

Elevated Plasmin(ogen) as a Common Risk Factor for COVID-19 Susceptibility

Proteolytic processing of the cilium adhesin MHJ_0194 (P123_J) inMycoplasma hyopneumoniaegenerates a functionally diverse array of cleavage fragments that bind multiple host molecules

Update onMycoplasma hyopneumoniaeinfections in pigs: Knowledge gaps for improved disease control

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Plasmin activity in the porcine airways is enhanced during experimental infection with Mycoplasma hyopneumoniae, is positively correlated with proinflammatory cytokine levels and is ameliorated by vaccination

Cited by 24 publications

References 33 publications

Elevated Plasmin(ogen) as a Common Risk Factor for COVID-19 Susceptibility

Elevated Plasmin(ogen) as a Common Risk Factor for COVID-19 Susceptibility

Proteolytic processing of the cilium adhesin MHJ_0194 (P123J) inMycoplasma hyopneumoniaegenerates a functionally diverse array of cleavage fragments that bind multiple host molecules

Update onMycoplasma hyopneumoniaeinfections in pigs: Knowledge gaps for improved disease control

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Proteolytic processing of the cilium adhesin MHJ_0194 (P123_J) inMycoplasma hyopneumoniaegenerates a functionally diverse array of cleavage fragments that bind multiple host molecules