{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T10:06:11Z","timestamp":1776161171081,"version":"3.50.1"},"reference-count":72,"publisher":"American Society of Hematology","issue":"15","license":[{"start":{"date-parts":[[2022,1,13]],"date-time":"2022-01-13T00:00:00Z","timestamp":1642032000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/legalcode"}],"content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,4,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Microvesicles (MVs) have previously been shown to exert profibrinolytic capacity, which is increased in patients with septic shock (SS) with a favorable outcome. We, therefore, hypothesized that the plasmin generation capacity (PGC) could confer to MVs a protective effect supported by their capacity to lyse a thrombus, and we investigated the mechanisms involved. Using an MV-PGC kinetic assay, ELISA, and flow cytometry, we found that granulocyte MVs (Gran-MVs) from SS patients display a heterogeneous PGC profile driven by the uPA (urokinase)\/uPAR system. In vitro, these MVs lyse a thrombus according to their MV-PGC levels in a uPA\/uPAR-dependent manner, as shown in a fluorescent clot lysis test and a lysis front retraction assay. Fibrinolytic activators conveyed by MVs contribute to approximately 30% of the plasma plasminogenolytic capacity of SS patients. In a murine model of SS, the injection of high PGC Gran-MVs significantly improved mouse survival and reduced the number of thrombi in vital organs. This was associated with a modification of the mouse coagulation and fibrinolysis properties toward a more fibrinolytic profile. Interestingly, mouse survival was not improved when soluble uPA was injected. Finally, using a multiplex array on plasma from SS patients, we found that neutrophil elastase correlates with the effect of high-PGC-capacity plasma and modulates the Gran-MV plasmin generation capacity by cleaving uPA-PAI-1 complexes. In conclusion, we show that the high PGC level displayed by Gran-MVs reduces thrombus formation and improves survival, conferring to Gran-MVs a protective role in a murine model of sepsis.<\/jats:p>","DOI":"10.1182\/blood.2021013328","type":"journal-article","created":{"date-parts":[[2022,1,13]],"date-time":"2022-01-13T19:54:41Z","timestamp":1642103681000},"page":"2377-2391","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":19,"title":["Granulocyte microvesicles with a high plasmin generation capacity promote clot lysis and improve outcome in septic shock"],"prefix":"10.1182","volume":"139","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6539-7879","authenticated-orcid":false,"given":"Sylvie","family":"Cointe","sequence":"first","affiliation":[{"name":"Aix-Marseille University, C2VN, INSERM 1263, INRA 1260, Marseille, France;"},{"name":"Department of Hematology and Vascular Biology, CHU La Conception, APHM, Marseille, France;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2460-4645","authenticated-orcid":false,"given":"Loris","family":"Vallier","sequence":"additional","affiliation":[{"name":"Aix-Marseille University, C2VN, INSERM 1263, INRA 1260, Marseille, France;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pierre","family":"Esnault","sequence":"additional","affiliation":[{"name":"Intensive Care Unit, Sainte Anne Military Hospital, Toulon, France;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mathilde","family":"Dacos","sequence":"additional","affiliation":[{"name":"Aix-Marseille University, C2VN, INSERM 1263, INRA 1260, Marseille, France;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amandine","family":"Bonifay","sequence":"additional","affiliation":[{"name":"Aix-Marseille University, C2VN, INSERM 1263, INRA 1260, Marseille, 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