Leukocyte‐Specific Protein 1 (LSP1) regulates neutrophil migration in acute lung inflammation

Abstract

LSP1, an F‐actin binding protein, plays a role in neutrophil recruitment in peritoneum. Because mechanisms of excessive migration of activated neutrophils, credited with tissue damage, are not fully understood, we explored the hitherto unknown expression and role of LSP1 in neutrophil migration in acute lung inflammation (ALI). We induced ALI through intranasal E. coli LPS (80μg) in wild type 129/SVJ (WT) and LSP1 deficient (LSP−/− ) mice. WT (n=10) and LSP−/− (n=11) mice showed significant neutrophilia and more neutrophils in broncho‐alveolar lavage (BAL) at 9 hr post‐LPS challenge compared to respective saline‐treated controls (WT=7; LSP−/−=10). BAL neutrophil numbers were higher in LPS‐treated WT mice compared to LSP−/− mice (P<0.001). Lung myeloperoxidase and Gr1+ were higher in LPS‐treated WT compared to the LSP−/− mice (P<0.05). Lung tissue and BAL fluid KC, MCP1, MIP1α and MIP1β concentration and vascular permeability were not different between LPS‐treated WT and LSP−/− mice but TNFα concentration was higher in LPS‐treated WT mice. LSP1 expression was increased in inflamed lungs from LPS‐treated mice, and autopsied lungs from septic humans, compared to their respective controls. H&E staining showed more septal congestion in LPS‐treated WT mice compared to LSP−/− mice. These data show that LSP1 expression is modulated in ALI and that LSP1 deficiency reduces neutrophil migration into ALI. Funding: NSERC