Integrin alpha 9 may play a role in modulating arterial thrombosis, according to a mouse model published in Blood.1
Previous research suggests that neutrophil depletion inhibits thrombosis. Neutrophil extracellular traps (NETs) — which contain chromatin and antimicrobial proteins — are promoted by activated platelets; there is evidence, furthermore, that NETs are involved in thrombosis formation by binding to plasma proteins, including von Willebrand factor.
Integrin alpha 9, which is expressed on neutrophils but absent on platelets, did not previously have a well-known role in arterial thrombosis. For this mouse model, researchers evaluated whether myeloid cell integrin alpha 9 modulates NET release, regulating arterial thrombosis formation. To do this, novel, myeloid cell–specific integrin alpha 9-/- mice were generated; alpha 9fl/fl were used as controls.
Compared with controls, the novel mouse group was less susceptible to arterial thrombosis in models using ferric chloride and laser injury–induced thrombosis. NETs were also found in a lower percentage of mice in the experimental group’s neutrophils stimulated with thrombin-activated platelets.
When the researchers transfused alpha 9fl/fl neutrophils into mice in the experimental group, thrombosis rates were similar in both groups.
“In summary, these findings identify a novel role for integrin [alpha] 9 in the modulation of arterial thrombosis,” the authors wrote.
Dhanesha N, Nayak MK, Doddapattar P, et al. Targeting myeloid-cell specific integrin α9β1 inhibits arterial thrombosis in mice. Blood. 2020;135(11):857-861.