Chauhan Anil K

Dhanesha Nirav

Doddapattar Prakash

Flora Gagan D

Jain Manish

Nayak Manasa K

今 重之

Dhanesha, Nirav

46971

Nayak, Manasa K

46977

Doddapattar, Prakash

46974

Jain, Manish

46972

Flora, Gagan D

46996

今, 重之

45524

コン, シゲユキ

Chauhan, Anil K

46980

Fukuyama University Repository / 福山大学学術情報リポジトリ

骨髄組織特異的インテグリンであるα9β1 の機能抑制は、マウス血栓を 抑制する  Nirav Dhanesha*, Manasa K Nayak*, Prakash Doddapattar*, Manish *, Gagan D Flora*,  今 重之, Anil K Chauhan*  Blood.135:857-861, 2020.  Targeting myeloid-cell specific integrin α9β1 inhibits arterial thrombosis in mice  Nirav Dhanesha, Manasa K Nayak, Prakash Doddapattar, Manish Jain, Gagan D Flora, Shigeyuki Kon, Anil K Chauhan  Abstract Evidence suggests that neutrophils contribute to thrombosis via several mechanisms, including neutrophil extracellular traps (NETs) formation. Integrin α9β1 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 α9 in arterial thrombosis remains unexplored. We generated novel myeloid cell-specific integrin α9-/- mice (α9fl/flLysMCre+) to study the role of integrin α9 in arterial thrombosis. α9fl/fl littermates were used as controls. We report that α9fl/flLysMCre+ 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 α9fl/flLysMCre+ 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 α9fl/flLysMCre+ mouse neutrophils stimulated with thrombin-activated platelets. Furthermore, we found a significant decrease in neutrophil-mediated platelet aggregation and cathepsin-G secretion in α9fl/flLysMCre+ mice. Transfusion of α9fl/fl neutrophils in α9fl/flLysMCre+ mice restored thrombosis similar to α9fl/fl mice. Treatment of wild-type mice with anti-integrin α9 antibody inhibited arterial thrombosis. This study identifies the potential role of integrin α9 in modulating arterial thrombosis.  抄録 骨髄細胞のα9インテグリンを特異的に欠損させたマウスでは、血栓を抑制できることが分かった。さらにα9インテグリンの中和抗体を用いても血栓を抑制できることが分かった。本結果から、動脈硬化にα9インテグリンが関与していることが分かった。  *Division of Hematology/Oncology, Department of Internal Medicine, University of Iowa, Iowa City, USA.     

Targeting myeloid-cell specific integrin α9β1 inhibits arterial thrombosis in mice

https://fukuyama-u.repo.nii.ac.jp/?action=repository_action_common_download&item_id=9189&item_no=1&attribute_id=18&file_no=1

骨髄組織特異的インテグリンであるα9β1 の機能抑制は、マウス血栓を抑制する

骨髄組織特異的インテグリンであるα9β1 の機能抑制は、マウス血栓を抑制する

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Fukuyama University Repository / 福山大学学術情報リポジトリ