دورية أكاديمية
Granulocyte microvesicles with a high plasmin generation capacity promote clot lysis and improve outcome in septic shock
| العنوان: | Granulocyte microvesicles with a high plasmin generation capacity promote clot lysis and improve outcome in septic shock |
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| المؤلفون: | Cointe, Sylvie, Vallier, Loris, Esnault, Pierre, Dacos, Mathilde, Bonifay, Amandine, Macagno, Nicolas, Harti Souab, Karim, Chareyre, Corinne, Judicone, Coralie, Frankel, Diane, Robert, Stéphane, Hraiech, Sami, Alessi, Marie-Christine, Poncelet, Philippe, Albanese, Jacques, Dignat-George, Françoise, Lacroix, Romaric |
| المساهمون: | Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital de la Conception CHU - APHM (LA CONCEPTION), Hopital d'instruction des armées Sainte-Anne Toulon (HIA), Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Anatomo-Cyto-Pathologie et de NeuroPathologie Hôpital de la Timone - APHM (ACPNP), Aix Marseille Université (AMU)-Hôpital de la Timone CHU - APHM (TIMONE), BioCytex SARL Marseille, Laboratoire de Biologie Cellulaire Hôpital de la Timone - APHM, Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Timone CHU - APHM (TIMONE), Hôpital Nord CHU - APHM, Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), Hôpital de la Timone CHU - APHM (TIMONE) |
| المصدر: | ISSN: 0006-4971. |
| بيانات النشر: | HAL CCSD American Society of Hematology |
| سنة النشر: | 2022 |
| المجموعة: | Institut National de la Recherche Agronomique: ProdINRA |
| مصطلحات موضوعية: | [SDV]Life Sciences [q-bio] |
| الوصف: | International audience ; Abstract 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. ; 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 ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/35026004; hal-03666657; https://amu.hal.science/hal-03666657Test; PUBMED: 35026004; WOS: 000793012200017 |
| DOI: | 10.1182/blood.2021013328 |
| الإتاحة: | https://doi.org/10.1182/blood.2021013328Test https://amu.hal.science/hal-03666657Test |
| رقم الانضمام: | edsbas.FCB697D5 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1182/blood.2021013328 |
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