Deficiency of Leukocyte‐Specific Protein 1 (LSP1) Alleviates Asthma in a Mouse Model

Abstract

Asthma is one of the most serious forms of respiratory disease, causing economic losses, high mortality, and morbidity globally. However, its etiology is still ambiguous. Many inflammatory cells, including T lymphocytes, eosinophils, mast cells, macrophages, and neutrophils, are recruited into the airway of asthma lung patients. In the previous study, we reported that LSP1 deficiency reduces neutrophil migration and acute lung inflammation, but its role in asthma remains unknown. Therefore, in this study, we developed an asthma‐like disease in LSP1‐deficient (Lsp1−/−) and wild‐type (WT) 129/SvJ mice (n=6 each treatment group) through two intraperitoneal (IP) injections of 2μg OVA/2mg alum two weeks apart, followed by three aerosol challenges with 1% OVA two days apart after two weeks of the last IP injection. We hypothesized that the absence of LSP1 inhibited airway inflammation in this OVA‐induced asthma mouse model due to inhibition of immune cell migration.Immunohistochemistry staining and western blot data showed that the level of LSP1 increased in asthma mouse lungs, compared with normal healthy lungs. Results from immuno‐gold as well as immunofluorescent staining illustrated that LSP1 was expressed on endothelium, bronchiolar epithelium, neutrophils, eosinophils, lymphocytes, alveolar macrophages, and pulmonary intravascular macrophages. There was no significant difference in peripheral leukocyte numbers between normal and asthmatic WT and Lsp1−/− mice. However, compared to Lsp1−/− asthma mice, WT asthma mice had higher levels leukocytes in broncho‐alveolar lavage fluid, higher myeloperoxidase, a marker of neutrophils, and eosiperoxidase levels in lungs (P<0.05). The level of OVA‐specific IgE, but not IgA and IgG1, in the serum of WT asthma mice was higher than that of Lsp1−/− asthma mice (P<0.05). Other research reported that IL‐4, IL‐5, IL‐6, IL‐13, and KC are associated with eosinophilia and neutrophil migration. We found that the absence of the LSP1 gene significantly reduced the levels of IL‐4, IL‐5, IL‐6, IL‐13, and KC (P<0.05) but not the levels of IL‐17, eotaxin, IFN‐gamma, and total protein in broncho‐alveolar lavage fluid. The airway hyper‐responsiveness response to methacholine in Lsp1−/− asthma mice was ameliorated compared to WT asthma mice (P<0.05). Histopathology evaluation findings showed more recruited inflammatory cells, as well as airway and blood vessel wall thickening, in the lungs of WT mice than in those of Lsp1−/− mice. These data indicate that LSP1 promotes airway inflammation associated with asthma in this mouse model. LSP1 may be a potential target for therapeutic intervention in allergic lung disease or asthma in humans.Support or Funding InformationWe thank to the Natural Science and Engineering Research Council (NSERC), Graduate Student Scholarship from Integrated Training Program in Infectious Disease, Food Safety and Public Policy (ITraP), Devolved Graduate Scholarship from Department of Veterinary Biomedical Sciences, and Graduate Student Scholarship from Western College of Veterinary Medicine, University of Saskatchewan, Canada for supporting this research. We thank Ms. LaRhonda Sobchishin for the technical support provided for the electron microscope technique and Ms. Eiko Kawamura for technical support in using a confocal microscope.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.