Coagulation factor V is a T-cell inhibitor expressed by leukocytes in COVID-19.

Coagulation factor V is a T-cell inhibitor expressed by leukocytes in COVID-19.

iScience (2022-03-01)

Jun Wang, Prasanti Kotagiri, Paul A Lyons, Rafia S Al-Lamki, Federica Mescia, Laura Bergamaschi, Lorinda Turner, Michael D Morgan, Fernando J Calero-Nieto, Karsten Bach, Nicole Mende, Nicola K Wilson, Emily R Watts, Patrick H Maxwell, Patrick F Chinnery, Nathalie Kingston, Sofia Papadia, Kathleen E Stirrups, Neil Walker, Ravindra K Gupta, David K Menon, Kieren Allinson, Sarah J Aitken, Mark Toshner, Michael P Weekes, James A Nathan, Sarah R Walmsley, Willem H Ouwehand, Mary Kasanicki, Berthold Göttgens, John C Marioni, Kenneth G C Smith, Jordan S Pober, John R Bradley

PMID35224470

ZUSAMMENFASSUNG

Clotting Factor V (FV) is primarily synthesized in the liver and when cleaved by thrombin forms pro-coagulant Factor Va (FVa). Using whole blood RNAseq and scRNAseq of peripheral blood mononuclear cells, we find that FV mRNA is expressed in leukocytes, and identify neutrophils, monocytes, and T regulatory cells as sources of increased FV in hospitalized patients with COVID-19. Proteomic analysis confirms increased FV in circulating neutrophils in severe COVID-19, and immunofluorescence microscopy identifies FV in lung-infiltrating leukocytes in COVID-19 lung disease. Increased leukocyte FV expression in severe disease correlates with T-cell lymphopenia. Both plasma-derived and a cleavage resistant recombinant FV, but not thrombin cleaved FVa, suppress T-cell proliferation in vitro. Anticoagulants that reduce FV conversion to FVa, including heparin, may have the unintended consequence of suppressing the adaptive immune system.

MATERIALIEN

Produktnummer

Marke

Produktbeschreibung

H0393

Sigma-Aldrich

Hirudin, recombinant, expressed in unspecified host, ≥7,000 ATU/mg protein (ATU = antithrombin units)