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SHR Neuro Cancer Cardio Lipid Metab Microb

Jandl, K; Berg, JL; Birnhuber, A; Fliesser, E; Borek, I; Seeliger, B; David, S; Schmidt, JJ; Gorkiewicz, G; Zacharias, M; Welte, T; Olschewski, H; Heinemann, A; Wygrecka, M; Kwapiszewska, G.
Basement membrane product, endostatin, as a link between inflammation, coagulation and vascular permeability in COVID-19 and non-COVID-19 acute respiratory distress syndrome.
Front Immunol. 2023; 14: 1188079 Doi: 10.3389/fimmu.2023.1188079 [OPEN ACCESS]
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Leading authors Med Uni Graz

Berg Johannes Lorenz

Jandl Katharina

Co-authors Med Uni Graz

Birnhuber Anna

Borek Izabela Malgorzata

Fließer Elisabeth

Gorkiewicz Gregor

Heinemann Akos

Kwapiszewska-Marsh Grazyna

Olschewski Horst

Zacharias Martin

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Abstract:

BACKGROUND: Immune 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. METHODS: In 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. RESULTS: We 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. CONCLUSION: The 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.

Find related publications in this database (using NLM MeSH Indexing)

Humans - administration & dosage

Endostatins - adverse effects, metabolism

Capillary Permeability - administration & dosage

Endothelial Cells - metabolism

COVID-19 - metabolism

Respiratory Distress Syndrome - pathology

Inflammation - metabolism

Find related publications in this database (Keywords)

extracellular matrix

matrikines

acute lung injury

neutrophils

endothelium

platelets

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