Journal article
Targeting myeloid-cell specific integrin alpha 9 beta 1 inhibits arterial thrombosis in mice
Blood, Vol.135(11), pp.857-861
03/12/2020
DOI: 10.1182/blood.2019002846
PMCID: PMC7068033
PMID: 31951649
Abstract
Evidence suggests that neutrophils contribute to thrombosis via several mechanisms, including neutrophil extracellular traps (NETs) formation. Integrin alpha 9 beta 1 is highly expressed on neutrophils when compared with monocytes. It undergoes affinity upregulation on neutrophil activation, and stabilizes adhesion to the activated endothelium. The role of integrin alpha 9 in arterial thrombosis remains unexplored. We generated novel myeloid cell- specific integrin alpha 9(-/-) mice (alpha 9(fl/ffl)LysMCre(+)) to study the role of integrin alpha 9 in arterial thrombosis. alpha 9(fl/ffl) littermates were used as controls. We report that alpha 9(fl/ffl)LysMCre(+) mice were less susceptible to arterial thrombosis in ferric chloride (FeCl3) and laser injury-induced thrombosis models with unaltered hemostasis. Neutrophil elastase-positive cells were significantly reduced in alpha 9(fl/ffl)LysMCre(+) mice concomitant with reduction in neutrophil count, myeloperoxidase levels, and red blood cells in the FeCl3 injury-induced carotid thrombus. The percentage of cells releasing NETs was significantly reduced in alpha 9(fl/ffl)LysMCre(+) mouse neutrophils stimulated with thrombin-activated platelets. Furthermore, we found a significant decrease in neutrophil-mediated platelet aggregation and cathepsin-G secretion in alpha 9(fl/ffl)LysMCre(+) mice. Transfusion of rir9filli neutrophils in alpha 9(fl/ffl)LysMCre(+) mice restored thrombosis similar to alpha 9(fl/ffl) mice. Treatment of wild-type mice with anti-integrin alpha 9 antibody inhibited arterial thrombosis. This study identifies the potential role of integrin alpha 9 in modulating arterial thrombosis.
Details
- Title: Subtitle
- Targeting myeloid-cell specific integrin alpha 9 beta 1 inhibits arterial thrombosis in mice
- Creators
- Nirav Dhanesha - University of IowaManasa K. Nayak - University of IowaPrakash Doddapattar - University of IowaManish Jain - University of IowaGagan D. Flora - University of IowaShigeyuki Kon - Fukuyama UniversityAnil K. Chauhan - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Blood, Vol.135(11), pp.857-861
- Publisher
- Amer Soc Hematology
- DOI
- 10.1182/blood.2019002846
- PMID
- 31951649
- PMCID
- PMC7068033
- ISSN
- 0006-4971
- eISSN
- 1528-0020
- Number of pages
- 5
- Grant note
- American Society of Hematology R01NS109910 / NIH, National Institute of Neurological Disorders and Stroke; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS) R35HL139926 / National Institutes of Health (NIH), National Heart, Lung, and Blood Institute; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) 18EIA33900009 / American Heart Association
- Language
- English
- Date published
- 03/12/2020
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984359783102771
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