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

ABSTRACT

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.

MATERIALS

Product Number

Brand

Product Description

H0393

Sigma-Aldrich

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