Role of macrophage inflammatory protein-1α (MIP-1α) in acute lung injury in rats

T. P. Shanley, H. Schmal, H. P. Friedl, M. L. Jones, P. A. Ward*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

165 Scopus citations

Abstract

The role of macrophage inflammatory protein-1α (MIP-1α) in the pathogenesis of acute lung injury in rats after intrapulmonary deposition of IgG immune complexes or intratracheal administration of LPS has been assessed. Critical to these studies was the cloning and functional expression of rat MIP-1α. The resulting product shared 92% and 90% homology with the known murine sequence at the cDNA level and protein level, respectively. Recombinant rat MIP-1α exhibited dose-dependent chemotactic activity for both rat and human monocytes and neutrophils, which could be blocked by anti- murine MIP-1α Ab. Rat MIP-1α mRNA and protein expression were determined as a function of time in both injury models. A time-dependent increase in MIP- 1α mRNA in lung extracts was observed in both models. In the LPS model, MIP- 1α protein could also be detected in bronchoalveolar lavage (BAL) fluids by Western blot analysis. Anti-MIP-1α administered at commencement of IgG immune complex- or LPS-induced injury resulted in significant reductions in BAL neutrophils as well as in injury as measured by pulmonary vascular permeability. Under such conditions, in both models TNF-α content in BAL fluids was substantially reduced as compared with BAL fluids from positive control animals. These findings suggest that rat MIP-1α plays an important role in the development of lung injury in these neutrophil-dependent models. The role of MIP-1α seems to be related to production of TNF-α, which in turn up-regulates vascular adhesion molecules required for neutrophil influx.

Original languageEnglish (US)
Pages (from-to)4793-4802
Number of pages10
JournalJournal of Immunology
Volume154
Issue number9
StatePublished - Jan 1 1995

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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