Murine cadherin‐6 mediates thrombosis in vivo in a platelet‐independent manner

Bouck, Emma G; Fuente, María de la; Zunica, Elizabeth R. M.; Li, Wei; Mumaw, Michele M.; Nieman, Marvin T.

doi:10.1002/rth2.12458

Cited by 3 publications

(2 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…At day 5, comparing isomAb to PD-L1mAb in infected animals at FDR10% ( Supplementary Table 3 , Figure 5D ), downregulated serum proteins are associated with apoptosis [Casp3, caspase 3 ( 59 )], Th2/eosinophil responses [IL-5 ( 60 )], and cellular function [Map2k6, mitogen-activated protein kinase kinase 6 ( 61 ); Wisp1, WNT1-inducible signaling pathway protein 1 ( 62 )]. Concomitantly, increased proteins were related to COVID-19 inflammation [Tnf ( 58 )], injury [Matn2 ( 56 )] and severity [Tnfsf12 ( 57 ); Vegfd ( 63 )], angiogenesis and endothelial cell growth [Vegfd ( 63 ); Flrt2, fibronectin leucine-rich transmembrane protein 2 ( 64 )], neuronal activity [Sez6L2 ( 51 ), Gfra1 ( 49 ), Igsf3 ( 53 ), Tnr ( 52 ), and contactins (Cntn1 and Cntn4) ( 65 )], thrombosis [cdh6, cadherin 6 ( 66 )], and cell growth and survival [Riox2, ribosomal oxygenase 2 ( 67 )].…”

Section: Resultsmentioning

confidence: 99%

“…Despite PD-L1mAb-induced increases in immune activation, weight gain, and O 2 Sat, survival was not affected. The lack of PD-L1mAb benefit may be due to PD-L1mAb-induced production of clotting factors [fibrinogen, D-dimer ( 18 ); cdh6 ( 66 )] and markers of injury [liver injury score, Matn2 ( 56 )]. We also identified molecular signs of tissue hypoxia, which is a confounding factor in the diagnosis and treatment of COVID-19 ( 97 ).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Anti-PD-L1 therapy altered inflammation but not survival in a lethal murine hepatitis virus-1 pneumonia model

Curran,

Cui,

et al. 2024

Front. Immunol.

View full text Add to dashboard Cite

IntroductionBecause prior immune checkpoint inhibitor (ICI) therapy in cancer patients presenting with COVID-19 may affect outcomes, we investigated the beta-coronavirus, murine hepatitis virus (MHV)-1, in a lethal pneumonia model in the absence (Study 1) or presence of prior programmed cell death ligand-1 (PD-L1) antibody (PD-L1mAb) treatment (Study 2). MethodsIn Study 1, animals were inoculated intratracheally with MHV-1 or vehicle and evaluated at day 2, 5, and 10 after infection. In Study 2, uninfected or MHV-1-infected animals were pretreated intraperitoneally with control or PD-L1-blocking antibodies (PD-L1mAb) and evaluated at day 2 and 5 after infection. Each study examined survival, physiologic and histologic parameters, viral titers, lung immunophenotypes, and mediator production.ResultsStudy 1 results recapitulated the pathogenesis of COVID-19 and revealed increased cell surface expression of checkpoint molecules (PD-L1, PD-1), higher expression of the immune activation marker angiotensin converting enzyme (ACE), but reduced detection of the MHV-1 receptor CD66a on immune cells in the lung, liver, and spleen. In addition to reduced detection of PD-L1 on all immune cells assayed, PD-L1 blockade was associated with increased cell surface expression of PD-1 and ACE, decreased cell surface detection of CD66a, and improved oxygen saturation despite reduced blood glucose levels and increased signs of tissue hypoxia. In the lung, PD-L1mAb promoted S100A9 but inhibited ACE2 production concomitantly with pAKT activation and reduced FOXO1 levels. PD-L1mAb promoted interferon-γ but inhibited IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) production, contributing to reduced bronchoalveolar lavage levels of eosinophils and neutrophils. In the liver, PD-L1mAb increased viral clearance in association with increased macrophage and lymphocyte recruitment and liver injury. PD-L1mAb increased the production of virally induced mediators of injury, angiogenesis, and neuronal activity that may play role in COVID-19 and ICI-related neurotoxicity. PD-L1mAb did not affect survival in this murine model. DiscussionIn Study 1 and Study 2, ACE was upregulated and CD66a and ACE2 were downregulated by either MHV-1 or PD-L1mAb. CD66a is not only the MHV-1 receptor but also an identified immune checkpoint and a negative regulator of ACE. Crosstalk between CD66a and PD-L1 or ACE/ACE2 may provide insight into ICI therapies. These networks may also play role in the increased production of S100A9 and neurological mediators in response to MHV-1 and/or PD-L1mAb, which warrant further study. Overall, these findings support observational data suggesting that prior ICI treatment does not alter survival in patients presenting with COVID-19.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Anti-PD-L1 therapy altered inflammation but not survival in a lethal murine hepatitis virus-1 pneumonia model

Curran,

Cui,

et al. 2024

Front. Immunol.

View full text Add to dashboard Cite

show abstract

Application of peripherally inserted central catheter in immune tolerance induction treatment of children with hemophilia A and accompanying inhibitors in China

Wang,

Liu,

Ding

et al. 2023

Hematology

View full text Add to dashboard Cite

Relationship between serum cadherin 6 and 11 levels and severe and early-onset preeclampsia: A pilot study

Güvey¹,

Çalışkan

Yurtçu

et al. 2022

tjod

View full text Add to dashboard Cite

Objective: Preeclampsia is a highly morbid disease of placental origin, life-threatening condition for both a pregnant woman and her fetus. Cadherin 6 and 11 are adhesion molecules that play an important role in trophoblastic development and placentation. In our study, we investigated the change in serum cadherin 6 and 11 levels in pregnant women with preeclampsia. Materials and Methods: Pregnant women with preeclampsia were selected and compared with healthy women (as a control group) for a one-year study. The serum alanine aminotransferase, aspartate aminotransferase, and cadherin levels 6 and 11 of participants were analyzed and compared. Results: A total of 189 pregnant women were subdivided into 2 groups as preeclamptic (n=94) and women with healthy pregnancy (n=95). The cadherin 6 and cadherin 11 levels of the preeclamptic patients were significantly higher than those in the control group (p=0.001), and they were found to be significantly higher mainly in patients with early-onset and severe preeclampsia group (p=0.001). The cut-off cadherin 6 and 11 values for severe preeclampsia were found as 98.174 ng/mL and 1.92 ng/mL; with sensitivity of 88.3% and 84% respectively (p=0.001). Conclusion: The data analysis showed elevated serum cadherin 6 and 11 levels associated with the severity and early onset of pre-eclampsia. Serum cadherin 6 and 11 levels can be a candidate marker for the prediction of preeclampsia.

show abstract

Murine cadherin‐6 mediates thrombosis in vivo in a platelet‐independent manner

Cited by 3 publications

References 29 publications

Anti-PD-L1 therapy altered inflammation but not survival in a lethal murine hepatitis virus-1 pneumonia model

Anti-PD-L1 therapy altered inflammation but not survival in a lethal murine hepatitis virus-1 pneumonia model

Application of peripherally inserted central catheter in immune tolerance induction treatment of children with hemophilia A and accompanying inhibitors in China

Relationship between serum cadherin 6 and 11 levels and severe and early-onset preeclampsia: A pilot study

Contact Info

Product

Resources

About