Requirements for αd in IgG immune complex-induced rat lung injury

Thomas P. Shanley, Roscoe L. Warner, Larry D. Crouch, Gregory N. Dietsch, Darcey L. Clark, Maggie M. O'Brien, W. Michael Gallatin, Peter A. Ward

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

αd is a newly cloned adhesion molecule that forms a heterodimer with CD18. The requirement for αd in IgG immune complex-induced lung injury in rats has been evaluated by the use of blocking polyclonal and monoclonal antibodies to rat αd. Using whole lung extracts, Northern and Western blot analyses have revealed up-regulation of mRNA and αd protein in inflamed lungs. Immunostaining has revealed the presence of αd in lung tissue and in alveolar macrophages as early as 1 h after initiation of the inflammatory reaction. When polyclonal rabbit Ab to rat αd was coinstilled into lung together with Ab to BSA, lung injury (as determined by leakage of [125I]albumin into lung parenchyma) was significantly diminished. In parallel, there was reduced accumulation of neutrophils recoverable in bronchoalveolar lavage (BAL) fluids. These findings were associated with reduced levels of TNF-α as well as NO2-/NO3- in BAL fluids. A hamster mAb to rat αd was also protective in this lung injury model. Anti-αd inhibited in vitro production of NO2-/NO3- by rat alveolar macrophages (stimulated with LPS and IFN-γ) by approximately 60%. These data suggest that, in the lung inflammatory model employed, αd up-regulation occurs in lung macrophages and is necessary for expression of TNF-a, recruitment of neutrophils, and full development of lung injury.

Original languageEnglish (US)
Pages (from-to)1014-1020
Number of pages7
JournalJournal of Immunology
Volume160
Issue number2
StatePublished - Jan 15 1998

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Shanley, T. P., Warner, R. L., Crouch, L. D., Dietsch, G. N., Clark, D. L., O'Brien, M. M., Gallatin, W. M., & Ward, P. A. (1998). Requirements for αd in IgG immune complex-induced rat lung injury. Journal of Immunology, 160(2), 1014-1020.