Src kinase inhibition with dasatinib impairs neutrophil function and clearance of Escherichia coli infection in a murine model of acute lung injury.

ABSTRACT:

Background

Neutrophils rapidly respond to and clear infection from tissues, but can also induce tissue damage through excessive degranulation, when acute inflammation proceeds unchecked. A number of key neutrophil functions, including adhesion-dependent degranulation, are controlled by src family kinases. Dasatinib is a potent src inhibitor used in treating patients with chronic myeloid leukaemia and treatment-resistant acute lymphoblastic leukaemia. We hypothesized that dasatinib would attenuate acute inflammation by inhibiting neutrophil recruitment, degranulation and endothelial cell injury, without impairing bacterial clearance, in a murine model of bacteria-induced acute lung injury. C57BL/6 mice received intratracheal Escherichia coli, and were treated with intraperitoneal da

SUBMITTER: Macfarlane JG 

PROVIDER: S-EPMC7597020 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature