Leukocyte-specific protein 1 regulates neutrophil recruitment in acute lung inflammation

American Journal of Physiology. Lung Cellular and Molecular Physiology
Nguyen Phuong Khanh LeBaljit Singh

Abstract

The mechanisms of excessive migration of activated neutrophils into inflamed lungs, credited with tissue damage, are not fully understood. We explored the hitherto unknown expression of leukocyte-specific protein 1 (LSP1) in human and mouse lungs and neutrophils and examined its role in neutrophil migration in acute lung inflammation. Autopsied septic human lungs showed increased LSP1 labeling in epithelium, endothelium, and leukocytes, including in their nuclei compared with normal lungs. We induced acute lung inflammation through intranasal administration of E. coli lipopolysaccharide (LPS) (80 μg) in LSP1-deficient (Lsp1(-/-)) and wild-type (WT) 129/SvJ mice. Immunocytochemistry and Western blots showed increased expression of LSP1 and phosphorylated LSP1 in lungs of LPS-treated WT mice. Histology showed more congestion, inflammation, and Gr-1(+) neutrophils in lung of WT mice than Lsp1(-/-) mice. LPS-treated WT mice had significantly more neutrophils in bronchoalveolar lavage (BAL) and myeloperoxidase levels in lungs compared with Lsp1(-/-) mice. However, there were no differences in lung tissue and BAL concentrations of keratinocyte-derived chemokine, monocyte chemoattractant protein-1, macrophage inflammatory protein-1α a...Continue Reading

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