A murine multiple-injury model for the study of thromboinflammation.

Autor:	MacArthur TA; From the Division of Vascular and Endovascular Surgery (T.A.M.), Mayo Clinic, Rochester, Minnesota; Division of Acute Care Surgery (J.G.), Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey; Division of Trauma, Critical Care, and Acute Care Surgery (S.M.N., R.T., M.S.P.), and Department of Biostatistics (G.M.S., K.R.B.), Mayo Clinic, Rochester, Minnesota; Division of Hematology (J.-F.D.), Bloodworks Northwest, University of Washington, Seattle, Washington; Department of Surgery (R.A.K.), R. Adams Cowley Shock Trauma Center, Baltimore, Maryland; Department of Biochemistry and Molecular Biology (M.T.A.), Mayo Clinic, Rochester; and Department of Internal Medicine (J.K.), University of Michigan, Ann Arbor, Minnesota., Goswami J, Navarro SM, Spears GM, Bailey KR, Thompson R, Dong JF, Kozar RA, Auton MT, Knight J, Park MS
Jazyk:	angličtina
Zdroj:	The journal of trauma and acute care surgery [J Trauma Acute Care Surg] 2024 Feb 01; Vol. 96 (2), pp. 203-208. Date of Electronic Publication: 2023 Nov 07.
DOI:	10.1097/TA.0000000000004179
Abstrakt:	Introduction: Neutrophil extracellular traps (NETs) contribute to trauma-induced coagulopathy. We aimed to develop a murine multiple-injury model that induces thrombo-inflammatory response, that is, NETosis and accelerated thrombin generation. Methods: Wild-type male mice (n = 10, aged 8-12 weeks) underwent multiple injuries (gastrocnemius crush, femur fracture, and laparotomy) and were compared with an uninjured control group (n = 10). Mice were euthanized by cardiac puncture performed 3 hours after injury. Whole blood samples were immediately processed to platelet poor plasma for thrombin generation kinetics (calibrated automated thrombogram), myeloperoxidase (MPO), and von Willebrand factor quantification. Immunohistochemistry of lung tissue was performed to assess for citrullinated histone 3 (CitH3) and MPO. A NETosis cluster was defined as 3+ neutrophils staining for CitH3 at 400× magnification (CitH3 cluster). Data were presented either as mean (SD) or median (interquartile range) with p < 0.05 significant. Sham and trauma treated animals were compared by the two-sample Wilcoxon rank-sum test. Results: Animals subjected to multiple injuries had accelerated thrombin generation compared with controls with greater peak height (61.3 [41.2-73.2] vs. 28.4 [19.5-37.5] nM, p = 0.035) and shorter time to peak (3.37 [2.81-3.81] vs. 4.5 [4.08-4.75] minutes, p = 0.046). Markers of neutrophil activation were greater following multiple injuries than in controls (MPO, 961.1 [858.1-1116.8] vs. 481.3 [438.0-648.9] ng/mL; p = 0.004). NETosis, as evidenced by the aforementioned defined number of CitH3 clusters in the lung, was greater in multiple-injury animals than in controls (mean [SD], 3 [2.9] vs. 0.2 [0.7]; p = 0.009). Conclusion: This is the first study to demonstrate that NETosis and accelerated thrombin generation can be induced using a murine multiple-injury model, as early as 3 hours following injury. (Copyright © 2023 American Association for the Surgery of Trauma.)
Databáze:	MEDLINE
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