| Title: |
Coagulation factor V is a T-cell inhibitor expressed by leukocytes in COVID-19 |
| Authors: |
Wang, J; Kotagiri, P; Lyons, PA; Al-Lamki, RS; Mescia, F; Bergamaschi, L; Turner, L; Morgan, MD; Calero-Nieto, FJ; Bach, K; Mende, N; Wilson, NK; Watts, ER; Maxwell, PH; Chinnery, PF; Kingston, N; Papadia, S; Stirrups, KE; Walker, N; Gupta, RK; Menon, DK; Allinson, K; Aitken, SJ; Toshner, M; Weekes, MP; Nathan, JA; Walmsley, SR; Ouwehand, WH; Kasanicki, M; Göttgens, B; Marioni, JC; Smith, KGC; Pober, JS; Bradley, JR |
| Publisher Information: |
CELL PRESS |
| Publication Year: |
2022 |
| Collection: |
The University of Melbourne: Digital Repository |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| ISSN: |
2589-0042 |
| Relation: |
https://hdl.handle.net/11343/308743 |
| Availability: |
https://hdl.handle.net/11343/308743 |
| Rights: |
https://creativecommons.org/licenses/by/4.0 ; CC BY |
| Accession Number: |
edsbas.98A27E38 |
| Database: |
BASE |