Role for macrophage inflammatory protein-2 in lipopolysaccharide-induced lung injury in rats

Hagen Schmal, Thomas P. Shanley, Michael L. Jones, Hans Peter Friedl, Peter A. Ward*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

192 Scopus citations

Abstract

Macrophage inflammatory protein-2 (MIP-2) is a C-X-C chemokine that possesses chemotactic activity for neutrophils. Rat MIP-2 was cloned and expressed as a 7.9-kDa peptide that exhibited dose-dependent neutrophil chemotactic activity at concentrations from 10 to 250 nM. Rabbit polyclonal Ab to the 7.9-kDa peptide showed reactivity by Western blot analysis and suppressed its in vitro chemotactic activity. Cross-desensitization chemotaxis experiments suggested that the chemotactic responses elicited by MIP-2 and the related chemokine, cytokine-induced neutrophil chemoattractant, may be mediated through a common receptor. Also, chemotactic responses to human GRO-α were blocked by exposure of human neutrophils to either GRO-α or rat MIP-2, suggesting conservation of this receptor-mediated response. After LPS instillation into rat lung, mRNA for MIP-2 was up-regulated in a time-dependent manner, peaking at 6 h. MIP-2 protein was detected in bronchoalveolar lavage fluids of these animals and a significant amount of chemotactic activity present in these fluids was attributed to MIP-2. On the basis of intrapulmonary instillation of Ab to MIP-2, neutrophil accumulation in lungs after airway instillation of LPS was found to be MIP-2-dependent. These data indicate that MIP-2 plays a significant role in LPS-induced inflammatory response in rat lungs and is required for the full recruitment of neutrophils.

Original languageEnglish (US)
Pages (from-to)1963-1972
Number of pages10
JournalJournal of Immunology
Volume156
Issue number5
StatePublished - Mar 1 1996

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint

Dive into the research topics of 'Role for macrophage inflammatory protein-2 in lipopolysaccharide-induced lung injury in rats'. Together they form a unique fingerprint.

Cite this