Lymphatic coagulation and neutrophil extracellular traps in lung-draining lymph nodes of COVID-19 decedents.

Autor:	MacDonald ME; Pritzker School for Molecular Engineering, University of Chicago, Chicago, IL.; Biophysical Sciences Program, University of Chicago, Chicago, IL., Weathered RK; Pritzker School for Molecular Engineering, University of Chicago, Chicago, IL., Stewart EC; Pritzker School for Molecular Engineering, University of Chicago, Chicago, IL.; Committee on Immunology, University of Chicago, Chicago, IL., Magold AI; Pritzker School for Molecular Engineering, University of Chicago, Chicago, IL., Mukherjee A; Pritzker School for Molecular Engineering, University of Chicago, Chicago, IL., Gurbuxani S; Department of Pathology, University of Chicago, Chicago, IL., Smith H; Department of Pathology, University of Chicago, Chicago, IL., McMullen P; Department of Pathology, University of Chicago, Chicago, IL., Mueller J; Department of Pathology, University of Chicago, Chicago, IL., Husain AN; Department of Pathology, University of Chicago, Chicago, IL., Salles CM; Pritzker School for Molecular Engineering, University of Chicago, Chicago, IL., Briquez PS; Pritzker School for Molecular Engineering, University of Chicago, Chicago, IL., Rouhani SJ; Department of Medicine, University of Chicago, Chicago, IL., Yu J; Department of Medicine, University of Chicago, Chicago, IL., Trujillo J; Department of Medicine, University of Chicago, Chicago, IL., Pyzer AR; Department of Medicine, University of Chicago, Chicago, IL., Gajewski TF; Committee on Immunology, University of Chicago, Chicago, IL.; Department of Medicine, University of Chicago, Chicago, IL.; Ben May Department of Cancer Research, University of Chicago, Chicago, IL., Sperling AI; Committee on Immunology, University of Chicago, Chicago, IL.; Ben May Department of Cancer Research, University of Chicago, Chicago, IL., Kilarski WW; Pritzker School for Molecular Engineering, University of Chicago, Chicago, IL., Swartz MA; Pritzker School for Molecular Engineering, University of Chicago, Chicago, IL.; Committee on Immunology, University of Chicago, Chicago, IL.; Ben May Department of Cancer Research, University of Chicago, Chicago, IL.
Jazyk:	angličtina
Zdroj:	Blood advances [Blood Adv] 2022 Dec 27; Vol. 6 (24), pp. 6249-6262.
DOI:	10.1182/bloodadvances.2022007798
Abstrakt:	Clinical manifestations of severe COVID-19 include coagulopathies that are exacerbated by the formation of neutrophil extracellular traps (NETs). Here, we report that pulmonary lymphatic vessels, which traffic neutrophils and other immune cells to the lung-draining lymph node (LDLN), can also be blocked by fibrin clots in severe COVID-19. Immunostained tissue sections from COVID-19 decedents revealed widespread lymphatic clotting not only in the lung but also in the LDLN, where the extent of clotting correlated with the presence of abnormal, regressed, or missing germinal centers (GCs). It strongly correlated with the presence of intralymphatic NETs. In mice, tumor necrosis factor α induced intralymphatic fibrin clots; this could be inhibited by DNase I, which degrades NETs. In vitro, TNF-α induced lymphatic endothelial cell upregulation of ICAM-1 and CXCL8, among other neutrophil-recruiting factors, as well as thrombomodulin downregulation; in decedents, lymphatic clotting in LDLNs. In a separate cohort of hospitalized patients, serum levels of Myeloperoxidase-DNA (MPO-DNA, a NET marker) inversely correlated with antiviral antibody titers, but D-dimer levels, indicative of blood thrombosis, did not correlate with either. Patients with high MPO-DNA but low D-dimer levels generated poor antiviral antibody titers. This study introduces lymphatic coagulation in lungs and LDLNs as a clinical manifestation of severe COVID-19 and suggests the involvement of NETosis of lymphatic-trafficking neutrophils. It further suggests that lymphatic clotting may correlate with impaired formation or maintenance of GCs necessary for robust antiviral antibody responses, although further studies are needed to determine whether and how lymphatic coagulation affects adaptive immune responses. (© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
Databáze:	MEDLINE
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