Neutrophil-specific Shp1 loss results in lethal pulmonary hemorrhage in mouse models of acute lung injury.

ABSTRACT: Acute respiratory distress syndrome (ARDS) is associated with significant morbidity and mortality, and neutrophils are critical to its pathogenesis. Neutrophil activation is closely regulated by inhibitory tyrosine phosphatases including Src homology region 2 domain-containing phosphatase-1 (Shp1). Here, we report that loss of neutrophil Shp1 in mice produced hyperinflammation and lethal pulmonary hemorrhage in sterile inflammation and pathogen-induced models of acute lung injury (ALI) through a Syk kinase-dependent mechanism. We observed large intravascular neutrophil clusters, perivascular inflammation, and excessive neutrophil extracellular traps in neutrophil-specific Shp1-KO mice, suggesting an underlying mechanism for the observed pulmonary hemorrhage. Targeted immunomodulation throu

SUBMITTER: Moussavi-Harami SF 

PROVIDER: S-EPMC11645157 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature