Role of macrophage inflammatory protein-2 in aspiration-induced lung injury

Thomas P. Shanley*, Neeti Vasi, Bruce A. Davidson, Nader D. Nader, Paul R. Knight, Nicholas Bless, Peter A. Ward, Kent J. Johnson

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

48 Scopus citations


Objective: To determine the role of the chemokine, macrophage inflammatory protein (MIP)-2, in the pathogenesis of aspiration-induced lung injury in the rat. Design: Prospective, randomized, controlled animal study. Setting: University research laboratories. Subjects: Adult, male Long-Evans rats. Interventions: Anesthetized rats underwent induction of lung injury by well-described models of aspiration triggered by intratracheal delivery of acid alone, gastric particles alone, or the combination. After injury, induction of MIP-2 messenger RNA in whole lungs and immunoreactive MIP-2 in bronchoalveolar lavage (BAL) fluids was determined. The contribution of MIP-2 to BAL fluid chemotactic activity was defined by using an in vitro chemotaxis assay. The in vitro effect of blocking MIP-2 on pulmonary vascular leak, BAL fluid neutrophils, PaO2/FIO2 ratio, and alveolar-arterial oxygen tension gradient in acid-induced lung injury was determined. Measurements and Main Results: Induction of MIP-2 messenger RNA and protein over time was observed in response to all three stimuli. A significant portion (25% to 41%) of the chemotactic activity in BAL fluids from injured rats was inhibited by anti- MIP-2 antibody. After acid injury, blocking of MIP-2 was associated with a 53% decrease in BAL fluid neutrophils and a 33% decrease in pulmonary vascular leak. Although acid injury both impaired oxygenation and increased venous admixture, in vivo blocking of MIP-2 was associated with improved oxygenation as well as decreased venous admixture. Conclusions: MIP-2 was up- regulated during the development of aspiration-induced lung injury in rats. MIP-2 contributed to lung accumulation of neutrophils via a chemotactic mechanism. Although oxygenation and venous admixture are worsened by acid- induced lung injury in vivo, blocking of MIP-2 at the onset of injury improved these physiologic alterations. Because the aspiration event often is witnessed, chemokines may be valid therapeutic targets for inhibiting the subsequent inflammatory response.

Original languageEnglish (US)
Pages (from-to)2437-2444
Number of pages8
JournalCritical care medicine
Issue number7
StatePublished - 2000


  • Acid aspiration
  • Chemokines
  • Lung injury
  • Macrophage inflammatory protein-2
  • Neutrophils
  • Particulate aspiration

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine


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