Leukocyte Engagement of Platelet Glycoprotein Ibα via the Integrin Mac-1 Is Critical for the Biological Response to Vascular Injury
- 8 November 2005
- journal article
- Published by Ovid Technologies (Wolters Kluwer Health) in Circulation
- Vol. 112 (19), 2993-3000
- https://doi.org/10.1161/circulationaha.105.571315
Abstract
Background— Leukocyte-platelet interactions are critical in the initiation and progression of atherosclerosis as well as restenosis. Although the leukocyte integrin Mac-1 (α M β 2 , CD11b/CD18) has been implicated in the firm adhesion and transmigration of leukocytes at sites of platelet deposition, the precise α M β 2 counterligand responsible for mediating adhesion-strengthening interactions between neutrophils and platelets in vivo has not previously been identified. Methods and Results— Our previous studies have established the P 201 -K 217 sequence in the α M I domain as the binding site for platelet glycoprotein (GP) Ibα. Here we report that antibody targeting of α M (P 201 -K 217 ) reduced α M β 2 -dependent adhesion to GP Ibα but not other α M β 2 ligands, including fibrinogen, intercellular adhesion molecule-1, and junctional adhesion molecule-3. Anti-α M (P 201 -K 217 ) inhibited the firm adhesion of both human and murine leukocytes to adherent platelets under laminar flow conditions. In a mouse femoral artery wire injury model, antibody targeting of α M (P 201 -K 217 ) reduced leukocyte accumulation after injury that was accompanied by inhibition of cellular proliferation and neointimal thickening. Conclusions— This study demonstrates that GP Ibα is a physiologically relevant ligand for α M β 2 and that integrin engagement of GP Ibα is critical to leukocyte function and the biological response to vascular injury. These observations establish a molecular target for selectively disrupting leukocyte-platelet complexes that promote inflammation in thrombosis and restenosis.Keywords
This publication has 28 references indexed in Scilit:
- Platelet P-selectin is required for pulmonary eosinophil and lymphocyte recruitment in a murine model of allergic inflammationBlood, 2005
- Targeting Platelet–Leukocyte InteractionsThe Journal of Experimental Medicine, 2003
- A Critical Role of Platelet Adhesion in the Initiation of Atherosclerotic Lesion FormationThe Journal of Experimental Medicine, 2002
- The Junctional Adhesion Molecule 3 (JAM-3) on Human Platelets is a Counterreceptor for the Leukocyte Integrin Mac-1The Journal of Experimental Medicine, 2002
- LFA-1 is sufficient in mediating neutrophil emigration in Mac-1-deficient mice.JCI Insight, 1997
- A functional integrin ligand on the surface of platelets: intercellular adhesion molecule-2.JCI Insight, 1994
- Traffic signals for lymphocyte recirculation and leukocyte emigration: The multistep paradigmCell, 1994
- Binding of the integrin Mac-1 (CD11b/CD18) to the third immunoglobulin-like domain of ICAM-1 (CD54) and its regulation by glycosylationCell, 1991
- Oligospecificity of the cellular adhesion receptor Mac-1 encompasses an inducible recognition specificity for fibrinogen.The Journal of cell biology, 1988
- Platelets in Glomerular DiseaseAnnual Review of Medicine, 1984