Published ahead of print on September 15, 2005, doi:10.1165/rcmb.2005-0093OC
© 2006 American Thoracic Society DOI: 10.1165/rcmb.2005-0093OC Gene Expression Profiles of Mst1r-Deficient Mice during Nickel-Induced Acute Lung InjuryDepartments of Surgery, Pediatrics, and Environmental Health and Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio Correspondence and requests for reprints should be addressed to Susan E. Waltz, Ph.D., Department of Surgery, University of Cincinnati College of Medicine, SRU/MSB G482 ML 0558, 231 Albert Sabin Way, Cincinnati, OH 45267-0558. E-mail: susan.waltz{at}uc.edu Previous studies have shown that mice deficient in the tyrosine kinase domain (TK–/–) of the receptor Mst1r have an increased susceptibility to nickel (Ni)-induced acute lung injury (ALI). Mst1r TK–/– mice have decreased survival times, alterations in cytokine and nitric oxide regulation, and an earlier onset of pulmonary pathology compared with control mice, suggesting that Mst1r signaling, in part, may regulate the response to ALI. To examine the role of Mst1r in ALI in more detail, we compared the gene expression profiles of murine lung mRNA from control and Mst1r TK–/– mice at baseline and after 24 h of particulate Ni sulfate exposure. Microarray analyses showed a total of 343 transcripts that were significantly changed, either by Ni treatment, or between genotypes. Genes responsible for inflammation, edema, and lymphocyte function were altered in the Mst1r TK–/– mice. Interestingly, the genes for several granzymes were increased in Mst1r TK–/– mice before Ni exposure, compared with controls. In addition, the Mst1r TK–/– lungs showed clusters of cells near the vascular endothelium and airways. Immunohistochemistry indicates these clusters are composed of macrophages, T cells, and neutrophils, and that the clusters display granzyme protein production. These results suggest that Mst1r signaling may be involved in the regulation of macrophage and T-lymphocyte activation in vivo during injury. This assessment of gene expression indicates the importance of genetic factors in contributing to lung injury, and points to strategies for intervention in the progression of inflammatory diseases.
Key Words: acute lung injury • gene expression arrays • hepatocyte growth factor–like protein • Mst1r • Ron receptor This article has been cited by other articles:
|
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
