Serpins in Venous Thrombosis and Venous Thrombus Resolution

Mukhopadhyay, Subhradip; Johnson, Tierra A.; Sarkar, Rajabrata; Antalis, Toni M.

doi:10.1007/978-1-4939-8645-3_13

Cited by 9 publications

(5 citation statements)

References 42 publications

(62 reference statements)

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“…Serine protease inhibitors can also act as potent inhibitors of thrombolytic serine proteases to modulate the in ammatory response (14). Thus, upregulation of the complement system with serine protease inhibitors is a manifestation of the involvement in the in ammatory response, indirectly causing the in ltration of heterophilic granulocytes.…”

Section: Discussionmentioning

confidence: 99%

Avian pathogenic Escherichia coli infection causes infiltration of heterophilic granulocytes of chick tracheal by the complement and coagulation cascades pathway

Zhao

Wang

et al. 2023

Preprint

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Background Avian pathogenic Escherichia coli (APEC) causes tracheal damage and heterophilic granulocytic infiltration and inflammation in infected chicks. In this study, we infected chick tracheal tissue with strain AE17 and produced pathological sections with proteomic sequencing. We compared the results of pathological sections from the APEC-infected group with those from the PBS control group; the pathological sections from the experimental group showed hemorrhage, fibrinization, and infiltration of heterophilic granulocytes in the tracheal tissue. To explore the effect on proteomics on inflammation and to further search for the caus. Results The tandem mass tag-based (TMT) sequencing analysis showed 224 upregulated and 140 downregulated proteins after infection with the AE17 strain. Based on the results of KEGG in Complement and coagulation cascades, differential protein expression in the Protein export pathway was upregulated. Conclusions With these results, we found that chemokines produced by the Complement and coagulation cascades pathway may cause infiltration of heterophilic granulocytes involved in inflammation, as well as antimicrobial factors produced by the complement system to fight the infection together.These results suggest that APEC causes the infiltration of heterophilic granulocytes through the involvement of the complement system with serine protease inhibitors.

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Section: Discussionmentioning

confidence: 99%

Avian pathogenic Escherichia coli infection causes infiltration of heterophilic granulocytes of chick tracheal by the complement and coagulation cascades pathway

Zhao

Wang

et al. 2023

Preprint

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“…This disease phenotype is similar to the phenotype we previously found in PAI-1-deficient ( Serpine1 −/− ) mice [ 7 ]. Like PAI-1, PAI-2 is considered to be an authentic and physiological inhibitor of uPA and tPA within extracellular environments [ 1 , 30 ]. Consequently, a lack of PAI-2 could lead to an increased formation of plasmin from plasminogen and thus to an imbalance between the coagulation and fibrinolysis system with an increased risk of bleeding.…”

Section: Discussionmentioning

confidence: 99%

The role of plasminogen activator inhibitor-2 in pneumococcal meningitis

Teske

Engelen-Lee

Dyckhoff-Shen

et al. 2022

acta neuropathol commun

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Pneumococcal meningitis is associated with dysregulation of the coagulation cascade. Previously, we detected upregulation of cerebral plasminogen activator inhibitor-2 (PAI-2) mRNA expression during pneumococcal meningitis. Diverse functions have been ascribed to PAI-2, but its role remains unclear. We analyzed the function of SERPINB2 (coding for PAI-2) in patients with bacterial meningitis, in a well-established pneumococcal meningitis mouse model, using Serpinb2 knockout mice, and in vitro in wt and PAI-2-deficient bone marrow-derived macrophages (BMDMs). We measured PAI-2 in cerebrospinal fluid of patients, and performed functional, histopathological, protein and mRNA expression analyses in vivo and in vitro. We found a substantial increase of PAI-2 concentration in CSF of patients with pneumococcal meningitis, and up-regulation and increased release of PAI-2 in mice. PAI-2 deficiency was associated with increased mortality in murine pneumococcal meningitis and cerebral hemorrhages. Serpinb2−/− mice exhibited increased C5a levels, but decreased IL-10 levels in the brain during pneumococcal infection. Our in vitro experiments confirmed increased expression and release of PAI-2 by wt BMDM and decreased IL-10 liberation by PAI-2-deficient BMDM upon pneumococcal challenge. Our data show that PAI-2 is elevated during in pneumococcal meningitis in humans and mice. PAI-2 deficiency causes an inflammatory imbalance, resulting in increased brain pathology and mortality.

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“…This is a robust model that accurately mimics many features of human DVT and it is well-established in the DVT literature (42–47). Stasis is induced by complete ligation of the inferior vena cava immediately below the renal veins, and all the side branches are either cauterized or ligated (48). The model produces thrombi of reproducible size and variation between animals is relatively small (Figure 2).…”

Section: Understanding Dvt and Its Resolution—animal Modelsmentioning

confidence: 99%

Fibrinolysis and Inflammation in Venous Thrombus Resolution

et al. 2019

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Clinical observations and accumulating laboratory evidence support a complex interplay between coagulation, inflammation, innate immunity and fibrinolysis in venous thromboembolism (VTE). VTE, which includes deep vein thrombosis (DVT) and pulmonary embolism (PE), and the subsequent complications of post-thrombotic syndrome (PTS), are significant causes of morbidity and mortality in patients. Clinical risk factors for VTE include cancer, major trauma, surgery, sepsis, inflammatory bowel disease, paralysis, prolonged periods of immobility, and aging. Abnormalities in venous blood flow or stasis initiates the activation of endothelial cells, and in concert with platelets, neutrophils and monocytes, propagates VTE in an intact vein. In addition, inflammatory cells play crucial roles in thrombus recanalization and restoration of blood flow via fibrinolysis and vascular remodeling. Faster resolution of the thrombus is key for improved disease prognosis. While in the clinical setting, anticoagulation therapy is successful in preventing propagation of venous thrombi, current therapies are not designed to inhibit inflammation, which can lead to the development of PTS. Animal models of DVT have provided many insights into the molecular and cellular mechanisms involved in the formation, propagation, and resolution of venous thrombi as well as the roles of key components of the fibrinolytic system in these processes. Here, we review the recent advances in our understanding of fibrinolysis and inflammation in the resolution of VTE.

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Serpins in Venous Thrombosis and Venous Thrombus Resolution

Cited by 9 publications

References 42 publications

Avian pathogenic Escherichia coli infection causes infiltration of heterophilic granulocytes of chick tracheal by the complement and coagulation cascades pathway

Avian pathogenic Escherichia coli infection causes infiltration of heterophilic granulocytes of chick tracheal by the complement and coagulation cascades pathway

The role of plasminogen activator inhibitor-2 in pneumococcal meningitis

Fibrinolysis and Inflammation in Venous Thrombus Resolution

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