| First Author | Wang Y | Year | 2017 |
| Journal | Nat Commun | Volume | 8 |
| Pages | 15559 | PubMed ID | 28555620 |
| Mgi Jnum | J:252241 | Mgi Id | MGI:5925208 |
| Doi | 10.1038/ncomms15559 | Citation | Wang Y, et al. (2017) Leukocyte integrin Mac-1 regulates thrombosis via interaction with platelet GPIbalpha. Nat Commun 8:15559 |
| abstractText | Inflammation and thrombosis occur together in many diseases. The leukocyte integrin Mac-1 (also known as integrin alphaMbeta2, or CD11b/CD18) is crucial for leukocyte recruitment to the endothelium, and Mac-1 engagement of platelet GPIbalpha is required for injury responses in diverse disease models. However, the role of Mac-1 in thrombosis is undefined. Here we report that mice with Mac-1 deficiency (Mac-1(-/-)) or mutation of the Mac-1-binding site for GPIbalpha 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:GPIbalpha inhibits thrombosis. Our data identify a new pathway of thrombosis involving leukocyte Mac-1 and platelet GPIbalpha, and suggest that targeting this interaction has anti-thrombotic therapeutic potential with reduced bleeding risk. |
