Deficiency of leukocyte-specific protein 1 (LSP1) alleviates asthmatic inflammation in a mouse model.

Abstract

BACKGROUND:

Asthma is a major cause of morbidity and mortality in humans. The mechanisms of asthma are still not fully understood. Leukocyte-specific protein-1 (LSP-1) regulates neutrophil migration during acute lung inflammation. However, its role in asthma remains unknown.

METHODS:

An OVA-induced mouse asthma model in LSP1-deficient (Lsp1-/-) and wild-type (WT) 129/SvJ mice were used to test the hypothesis that the absence of LSP1 would inhibit airway hyperresponsiveness and lung inflammation.

RESULTS:

Light and electron microscopic immunocytochemistry and Western blotting showed that, compared with normal healthy lungs, the levels of LSP1 were increased in lungs of OVA-asthmatic mice. Compared to Lsp1-/- OVA mice, WT OVA mice had higher levels of leukocytes in broncho-alveolar lavage fluid and in the lung tissues (P < 0.05). The levels of OVA-specific IgE but not IgA and IgG1 in the serum of WT OVA mice was higher than that of Lsp1-/- OVA mice (P < 0.05). Deficiency of LSP1 significantly reduced the levels of IL-4, IL-5, IL-6, IL-13, and CXCL1 (P < 0.05) but not total proteins in broncho-alveolar lavage fluid in asthmatic mice. The airway hyper-responsiveness to methacholine in Lsp1-/- OVA mice was improved compared to WT OVA mice (P < 0.05). Histology revealed more inflammation (inflammatory cells, and airway and blood vessel wall thickening) in the lungs of WT OVA mice than in those of Lsp1-/- OVA mice. Finally, immunohistology showed localization of LSP1 protein in normal and asthmatic human lungs especially associated with the vascular endothelium and neutrophils.

CONCLUSION:

These data show that LSP1 deficiency reduces airway hyper-responsiveness and lung inflammation, including leukocyte recruitment and cytokine expression, in a mouse model of asthma.

• Authors: Nguyen Phuong Khanh Le, Amanda Florentina do Nascimento, David Schneberger, Chi Cuong Quach, Xiaobei Zhang, Gurpreet K Aulakh, Wojciech Dawicki, Lixin Liu, John R Gordon, Baljit Singh
• Journal: Respiratory research (Respir Res) Vol. 23 Issue 1 Pg. 165 (Jun 22 2022) ISSN: 1465-993X [Electronic] England
• PMID: 35733161 (Publication Type: Journal Article)
• Copyright: © 2022. The Author(s).

Chemical References

• Ovalbumin

Topics

• Animals
• Asthma (metabolism)
• Bronchoalveolar Lavage Fluid
• Disease Models, Animal
• Inflammation (metabolism)
• Lung (metabolism)
• Mice
• Mice, Inbred BALB C
• Neutrophils (metabolism)
• Ovalbumin (toxicity)
• Respiratory Hypersensitivity (metabolism)