Frontiers in Immunology (May 2023)

Basement membrane product, endostatin, as a link between inflammation, coagulation and vascular permeability in COVID-19 and non-COVID-19 acute respiratory distress syndrome

  • Katharina Jandl,
  • Katharina Jandl,
  • Johannes Lorenz Berg,
  • Johannes Lorenz Berg,
  • Anna Birnhuber,
  • Anna Birnhuber,
  • Elisabeth Fliesser,
  • Izabela Borek,
  • Benjamin Seeliger,
  • Sascha David,
  • Julius J. Schmidt,
  • Gregor Gorkiewicz,
  • Martin Zacharias,
  • Tobias Welte,
  • Horst Olschewski,
  • Horst Olschewski,
  • Akos Heinemann,
  • Malgorzata Wygrecka,
  • Malgorzata Wygrecka,
  • Grazyna Kwapiszewska,
  • Grazyna Kwapiszewska,
  • Grazyna Kwapiszewska

DOI
https://doi.org/10.3389/fimmu.2023.1188079
Journal volume & issue
Vol. 14

Abstract

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BackgroundImmune cell recruitment, endothelial cell barrier disruption, and platelet activation are hallmarks of lung injuries caused by COVID-19 or other insults which can result in acute respiratory distress syndrome (ARDS). Basement membrane (BM) disruption is commonly observed in ARDS, however, the role of newly generated bioactive BM fragments is mostly unknown. Here, we investigate the role of endostatin, a fragment of the BM protein collagen XVIIIα1, on ARDS associated cellular functions such as neutrophil recruitment, endothelial cell barrier integrity, and platelet aggregation in vitro.MethodsIn our study we analyzed endostatin in plasma and post-mortem lung specimens of patients with COVID-19 and non-COVID-19 ARDS. Functionally, we investigated the effect of endostatin on neutrophil activation and migration, platelet aggregation, and endothelial barrier function in vitro. Additionally, we performed correlation analysis for endostatin and other critical plasma parameters.ResultsWe observed increased plasma levels of endostatin in our COVID-19 and non-COVID-19 ARDS cohort. Immunohistochemical staining of ARDS lung sections depicted BM disruption, alongside immunoreactivity for endostatin in proximity to immune cells, endothelial cells, and fibrinous clots. Functionally, endostatin enhanced the activity of neutrophils, and platelets, and the thrombin-induced microvascular barrier disruption. Finally, we showed a positive correlation of endostatin with soluble disease markers VE-Cadherin, c-reactive protein (CRP), fibrinogen, and interleukin (IL)-6 in our COVID-19 cohort.ConclusionThe cumulative effects of endostatin on propagating neutrophil chemotaxis, platelet aggregation, and endothelial cell barrier disruption may suggest endostatin as a link between those cellular events in ARDS pathology.

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