The role of the receptor tyrosine kinase Ron in nickel-induced acute lung injury

S. A. McDowell, A. Mallakin, C. J. Bachurski, K. Toney-Earley, D. R. Prows, T. Bruno, K. H. Kaestner, D. P. Witte, H. Melin-Aldana, S. J F Degen, G. D. Leikauf, S. E. Waltz*

*Corresponding author for this work

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

Acute lung injury (ALI), a severe respiratory syndrome, develops in response to numerous insults and responds poorly to therapeutic intervention. Recently, cDNA microarray analyses were performed that indicated several pathogenic responses during nickel-induced ALI, including marked macrophage activation. Macrophage activation is mediated, in part, via the receptor tyrosine kinase Ron. To address the role of Ron in ALI, the response of mice deficient in the cytoplasmic domain of Ron (Ron tk-/-) were assessed in response to nickel exposure. Ron tk-/- mice succumb to nickel-induced ALI earlier, express larger, early increases in interleukin-6, monocyte chemoattractant protein-1, and macrophage inflammatory protein-2, display greater serum nitrite levels, and exhibit earlier onset of pulmonary pathology and augmented pulmonary tyrosine nitrosylation. Increases in cytokine expression and cellular nitration can lead to tissue damage and are consistent with the differences between genotypes in the early onset of pathology and mortality in Ron tk-/- mice. These analyses indicate a role for the tyrosine kinase receptor Ron in ALI.

Original languageEnglish (US)
Pages (from-to)99-104
Number of pages6
JournalAmerican journal of respiratory cell and molecular biology
Volume26
Issue number1
DOIs
StatePublished - 2002

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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    McDowell, S. A., Mallakin, A., Bachurski, C. J., Toney-Earley, K., Prows, D. R., Bruno, T., Kaestner, K. H., Witte, D. P., Melin-Aldana, H., Degen, S. J. F., Leikauf, G. D., & Waltz, S. E. (2002). The role of the receptor tyrosine kinase Ron in nickel-induced acute lung injury. American journal of respiratory cell and molecular biology, 26(1), 99-104. https://doi.org/10.1165/ajrcmb.26.1.4621