Emily Janus-Bell, Nicolas Receveur, Luc Mercier, Clarisse Mouriaux, Stéphanie Magnenat, Jochen Reiser, François Lanza, Béatrice Hechler, Benoit Ho-Tin-Noé, Pierre H Mangin
{"title":"小鼠血小板β1和β3整合素在炎症条件下止血过程中的协同作用","authors":"Emily Janus-Bell, Nicolas Receveur, Luc Mercier, Clarisse Mouriaux, Stéphanie Magnenat, Jochen Reiser, François Lanza, Béatrice Hechler, Benoit Ho-Tin-Noé, Pierre H Mangin","doi":"10.1161/ATVBAHA.124.321104","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Platelets prevent bleeding in a variety of inflammatory settings, the adhesion receptors and activation pathways involved being highly context-dependent and functionally redundant. In some situations, platelets recruited to inflammatory sites act independently of aggregation. The mechanisms underlying stable platelet adhesion in inflamed microvessels remain incompletely understood, in particular, whether and if so, how β1 and β3 integrins are involved.</p><p><strong>Methods: </strong>The impact of isolated or combined platelet deficiency in β1 and β3 integrins on inflammation-associated hemostasis was investigated in 3 models of acute inflammation: immune complex-based cutaneous reverse passive Arthus reaction, intranasal lipopolysaccharide-induced lung inflammation, and cerebral ischemia-reperfusion following transient (2-hour) occlusion of the transient middle cerebral artery.</p><p><strong>Results: </strong>Mice with platelet-directed inactivation of <i>Itgb1</i> (PF4Cre-β1<sup>-/-</sup>) displayed no bleeding in any of the inflammation models, while mice defective in platelet <i>Itgb3</i> (PF4Cre-β3<sup>-/-</sup>) exhibited bleeding in all 3 models. Remarkably, the bleeding phenotype of PF4Cre-β3<sup>-/</sup><sup>-</sup> mice was exacerbated in the reverse passive Arthus model by the concomitant deletion of β1 integrins, PF4Cre-β1<sup>-/-</sup>/β3<sup>-/-</sup> animals presenting increased bleeding. Intravital microscopy in reverse passive Arthus experiments highlighted a major defect in the adhesion of PF4Cre-β1<sup>-/-</sup>/β3<sup>-/-</sup> platelets to inflamed microvessels. Unlike PF4Cre-β1<sup>-/-</sup> and PF4Cre-β3<sup>-/-</sup> mice, PF4Cre-β1<sup>-/-</sup>/β3<sup>-/-</sup> animals developed early hemorrhagic transformation 6 hours after transient middle cerebral artery occlusion. PF4Cre-β1<sup>-/-</sup>/β3<sup>-/-</sup> mice displayed no more bleeding in lipopolysaccharide-induced lung inflammation than PF4Cre-β3<sup>-/-</sup> animals.</p><p><strong>Conclusions: </strong>Altogether, these results show that the requirement for and degree of functional redundancy between platelet β1 and β3 integrins in inflammation-associated hemostasis vary with the inflammatory situation.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":null,"pages":null},"PeriodicalIF":7.4000,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Cooperation Between Platelet β1 and β3 Integrins in the Arrest of Bleeding Under Inflammatory Conditions in Mice.\",\"authors\":\"Emily Janus-Bell, Nicolas Receveur, Luc Mercier, Clarisse Mouriaux, Stéphanie Magnenat, Jochen Reiser, François Lanza, Béatrice Hechler, Benoit Ho-Tin-Noé, Pierre H Mangin\",\"doi\":\"10.1161/ATVBAHA.124.321104\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Platelets prevent bleeding in a variety of inflammatory settings, the adhesion receptors and activation pathways involved being highly context-dependent and functionally redundant. In some situations, platelets recruited to inflammatory sites act independently of aggregation. The mechanisms underlying stable platelet adhesion in inflamed microvessels remain incompletely understood, in particular, whether and if so, how β1 and β3 integrins are involved.</p><p><strong>Methods: </strong>The impact of isolated or combined platelet deficiency in β1 and β3 integrins on inflammation-associated hemostasis was investigated in 3 models of acute inflammation: immune complex-based cutaneous reverse passive Arthus reaction, intranasal lipopolysaccharide-induced lung inflammation, and cerebral ischemia-reperfusion following transient (2-hour) occlusion of the transient middle cerebral artery.</p><p><strong>Results: </strong>Mice with platelet-directed inactivation of <i>Itgb1</i> (PF4Cre-β1<sup>-/-</sup>) displayed no bleeding in any of the inflammation models, while mice defective in platelet <i>Itgb3</i> (PF4Cre-β3<sup>-/-</sup>) exhibited bleeding in all 3 models. Remarkably, the bleeding phenotype of PF4Cre-β3<sup>-/</sup><sup>-</sup> mice was exacerbated in the reverse passive Arthus model by the concomitant deletion of β1 integrins, PF4Cre-β1<sup>-/-</sup>/β3<sup>-/-</sup> animals presenting increased bleeding. Intravital microscopy in reverse passive Arthus experiments highlighted a major defect in the adhesion of PF4Cre-β1<sup>-/-</sup>/β3<sup>-/-</sup> platelets to inflamed microvessels. Unlike PF4Cre-β1<sup>-/-</sup> and PF4Cre-β3<sup>-/-</sup> mice, PF4Cre-β1<sup>-/-</sup>/β3<sup>-/-</sup> animals developed early hemorrhagic transformation 6 hours after transient middle cerebral artery occlusion. PF4Cre-β1<sup>-/-</sup>/β3<sup>-/-</sup> mice displayed no more bleeding in lipopolysaccharide-induced lung inflammation than PF4Cre-β3<sup>-/-</sup> animals.</p><p><strong>Conclusions: </strong>Altogether, these results show that the requirement for and degree of functional redundancy between platelet β1 and β3 integrins in inflammation-associated hemostasis vary with the inflammatory situation.</p>\",\"PeriodicalId\":8401,\"journal\":{\"name\":\"Arteriosclerosis, Thrombosis, and Vascular Biology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":7.4000,\"publicationDate\":\"2024-08-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Arteriosclerosis, Thrombosis, and Vascular Biology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1161/ATVBAHA.124.321104\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"HEMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Arteriosclerosis, Thrombosis, and Vascular Biology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1161/ATVBAHA.124.321104","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"HEMATOLOGY","Score":null,"Total":0}
Cooperation Between Platelet β1 and β3 Integrins in the Arrest of Bleeding Under Inflammatory Conditions in Mice.
Background: Platelets prevent bleeding in a variety of inflammatory settings, the adhesion receptors and activation pathways involved being highly context-dependent and functionally redundant. In some situations, platelets recruited to inflammatory sites act independently of aggregation. The mechanisms underlying stable platelet adhesion in inflamed microvessels remain incompletely understood, in particular, whether and if so, how β1 and β3 integrins are involved.
Methods: The impact of isolated or combined platelet deficiency in β1 and β3 integrins on inflammation-associated hemostasis was investigated in 3 models of acute inflammation: immune complex-based cutaneous reverse passive Arthus reaction, intranasal lipopolysaccharide-induced lung inflammation, and cerebral ischemia-reperfusion following transient (2-hour) occlusion of the transient middle cerebral artery.
Results: Mice with platelet-directed inactivation of Itgb1 (PF4Cre-β1-/-) displayed no bleeding in any of the inflammation models, while mice defective in platelet Itgb3 (PF4Cre-β3-/-) exhibited bleeding in all 3 models. Remarkably, the bleeding phenotype of PF4Cre-β3-/- mice was exacerbated in the reverse passive Arthus model by the concomitant deletion of β1 integrins, PF4Cre-β1-/-/β3-/- animals presenting increased bleeding. Intravital microscopy in reverse passive Arthus experiments highlighted a major defect in the adhesion of PF4Cre-β1-/-/β3-/- platelets to inflamed microvessels. Unlike PF4Cre-β1-/- and PF4Cre-β3-/- mice, PF4Cre-β1-/-/β3-/- animals developed early hemorrhagic transformation 6 hours after transient middle cerebral artery occlusion. PF4Cre-β1-/-/β3-/- mice displayed no more bleeding in lipopolysaccharide-induced lung inflammation than PF4Cre-β3-/- animals.
Conclusions: Altogether, these results show that the requirement for and degree of functional redundancy between platelet β1 and β3 integrins in inflammation-associated hemostasis vary with the inflammatory situation.
期刊介绍：
The journal "Arteriosclerosis, Thrombosis, and Vascular Biology" (ATVB) is a scientific publication that focuses on the fields of vascular biology, atherosclerosis, and thrombosis. It is a peer-reviewed journal that publishes original research articles, reviews, and other scholarly content related to these areas. The journal is published by the American Heart Association (AHA) and the American Stroke Association (ASA).
The journal was published bi-monthly until January 1992, after which it transitioned to a monthly publication schedule. The journal is aimed at a professional audience, including academic cardiologists, vascular biologists, physiologists, pharmacologists and hematologists.
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