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https://hdl.handle.net/2440/80608
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Type: | Journal article |
Title: | The CXCR1/2 ligand NAP-2 promotes directed intravascular leukocyte migration through platelet thrombi |
Author: | Ghasemzadeh, M. Kaplan, Z. Alwis, I. Schoenwaelder, S. Ashworth, K. Westein, E. Hosseini, E. Salem, H. Slattery, R. McColl, S. Hickey, M. Ruggeri, Z. Yuan, Y. Jackson, S. |
Citation: | Blood, 2013; 121(22):4555-4566 |
Publisher: | Amer Soc Hematology |
Issue Date: | 2013 |
ISSN: | 0006-4971 1528-0020 |
Statement of Responsibility: | Mehran Ghasemzadeh, Zane S. Kaplan, Imala Alwis, Simone M. Schoenwaelder, Katrina J. Ashworth, Erik Westein, Ehteramolsadat Hosseini, Hatem H. Salem, Robyn Slattery, Shaun R. McColl, Michael J. Hickey, Zaverio M. Ruggeri, Yuping Yuan and Shaun P. Jackson |
Abstract: | Thrombosis promotes leukocyte infiltration into inflamed tissues, leading to organ injury in a broad range of diseases; however, themechanisms by which thrombi guide leukocytes to sites of vascular injury remain ill-defined. Using mouse models of endothelial injury (traumatic or ischemia reperfusion), we demonstrate a distinct process of leukocyte recruitment, termed “directed intravascular migration,” specifically mediated by platelet thrombi. Single adherent platelets and platelet aggregates stimulated leukocyte shape change at sites of endothelial injury; however, only thrombi were capable of inducing directed intravascular leukocyte migration. Leukocyte recruitment and migration induced by platelet thrombi occurred most prominently in veins but could also occur in arteries following ischemia-reperfusion injury. In vitro studies demonstrated a major role for platelet-derived NAP-2 (CXCL-7) and its CXCR1/2 receptor in regulating leukocyte polarization and motility. In vivo studies demonstrated the presence of an NAP-2 chemotactic gradient within the thrombus body. Pharmacologic blockade of CXCR1/2 as well as genetic deletion of NAP-2 markedly reduced leukocyte shape change and intrathrombus migration. These studies define a distinct process of leukocyte migration that is initiated by homotypic adhesive interactions between platelets, leading to the development of an NAP-2 chemotactic gradient within the thrombus body that guides leukocytes to sites of vascular injury |
Keywords: | Mesenteric Arteries Blood Platelets Leukocytes Neutrophils Animals Mice, Inbred C57BL Mice, Transgenic Mice Thrombosis Reperfusion Injury Needlestick Injuries Green Fluorescent Proteins Receptors, Interleukin-8A Receptors, Interleukin-8B Chemokines, CXC Cell Adhesion Cell Movement Cell Polarity |
Rights: | © 2013 by The American Society of Hematology |
DOI: | 10.1182/blood-2012-09-459636 |
Grant ID: | ARC |
Published version: | http://dx.doi.org/10.1182/blood-2012-09-459636 |
Appears in Collections: | Aurora harvest 4 Molecular and Biomedical Science publications |
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