Тип публикации: статья из журнала

Год издания: 2017

Идентификатор DOI: 10.1038/ncomms15559

Ключевые слова: arachidonic acid, 506-32-1, 6610-25-9, 7771-44-0, collagen, 9007-34-5, fibrinogen, 9001-32-5, glucosamine, 3416-24-8, 4607-22-1, intercellular adhesion molecule 1, 126547-89-5, phorbol 13 acetate 12 myristate, 16561-29-8, protein, 67254-75-5, protein kinase C, 141436-78-4, thrombin, 9002-04-4, 869858-13-9

Аннотация: Inflammation and thrombosis occur together in many diseases. The leukocyte integrin Mac-1 (also known as integrin αMβ2, or CD11b/CD18) is crucial for leukocyte recruitment to the endothelium, and Mac-1 engagement of platelet GPIbα is required for injury responses in diverse disease models. However, the role of Mac-1 in thrombosis iПоказать полностьюs undefined. Here we report that mice with Mac-1 deficiency (Mac-1-/-) or mutation of the Mac-1-binding site for GPIbα have delayed thrombosis after carotid artery and cremaster microvascular injury without affecting parameters of haemostasis. Adoptive wild-type leukocyte transfer rescues the thrombosis defect in Mac-1-/- mice, and Mac-1-dependent regulation of the transcription factor Foxp1 contributes to thrombosis as evidenced by delayed thrombosis in mice with monocyte-/macrophage-specific overexpression of Foxp1. Antibody and small-molecule targeting of Mac-1:GPIbα inhibits thrombosis. Our data identify a new pathway of thrombosis involving leukocyte Mac-1 and platelet GPIbα, and suggest that targeting this interaction has anti-thrombotic therapeutic potential with reduced bleeding risk. © The Author(s) 2017.

Журнал: Nature Communications

Выпуск журнала: Vol. 8

Номера страниц: 15559

ISSN журнала: 20411723

Издатель: Nature Publishing Group

• Wang Y. (Case Cardiovascular Research Institute, Case Western Reserve University School of Medicine, Harrington Heart and Vascular Institute, University Hospitals Cleveland Medical Center, Cleveland, OH, United States)
• Gao H. (Case Cardiovascular Research Institute, Case Western Reserve University School of Medicine, Harrington Heart and Vascular Institute, University Hospitals Cleveland Medical Center, Cleveland, OH, United States)
• Shi C. (Case Cardiovascular Research Institute, Case Western Reserve University School of Medicine, Harrington Heart and Vascular Institute, University Hospitals Cleveland Medical Center, Cleveland, OH, United States)
• Erhardt P.W. (Department of Medicinal and Biological Chemistry, University of Toledo College of Pharmacy and Pharmaceutical Sciences, Toledo, OH, United States)
• Pavlovsky A. (Department of Medicinal and Biological Chemistry, University of Toledo College of Pharmacy and Pharmaceutical Sciences, Toledo, OH, United States)
• Soloviev D.A. (Department of Molecular Cardiology, Cleveland Clinic, Cleveland, OH, United States)
• Bledzka K. (Department of Molecular Cardiology, Cleveland Clinic, Cleveland, OH, United States)
• Ustinov V. (Department of Molecular Cardiology, Cleveland Clinic, Cleveland, OH, United States, Federal State Scientific Institute, Federal Research Centre Coal and Coal Chemistry, Siberian Branch of the Russian Academy of Sciences, Institute of Human Ecology, Kemerovo, Russian Federation)
• Zhu L. (Department of Molecular Cardiology, Cleveland Clinic, Cleveland, OH, United States)
• Qin J. (Department of Molecular Cardiology, Cleveland Clinic, Cleveland, OH, United States)
• Munday A.D. (Bloodworks Northwest Research Institute, Seattle, WA, United States)
• Lopez J. (Bloodworks Northwest Research Institute, Seattle, WA, United States)
• Plow E. (Department of Molecular Cardiology, Cleveland Clinic, Cleveland, OH, United States)
• Simon D.I. (Case Cardiovascular Research Institute, Case Western Reserve University School of Medicine, Harrington Heart and Vascular Institute, University Hospitals Cleveland Medical Center, Cleveland, OH, United States)

• Scopus