In vivo evidence for the role of GM-CSF as a mediator in acute pancreatitis-associated lung injury

Jean Louis Frossard, Ashok K. Saluja, Nicolas Mach, Hong Sik Lee, Lakshmi Bhagat, Antoine Hadenque, Laura Rubbia-Brandt, Glenn Dranoff, Michael L. Steer

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

Severe pancreatitis is frequently associated with acute lung injury (ALI) and the respiratory distress syndrome. The role of granulocyte-macrophage colony-stimulating factor (GM-CSF) in mediating the ALI associated with secretagogue-induced experimental pancreatitis was evaluated with GM-CSF knockout mice (GM-CSF -/-). Pancreatitis was induced by hourly (12x) intraperitoneal injection of a supramaximally stimulating dose of the cholecystokinin analog caerulein. The resulting pancreatitis was similar in GM-CSF-sufficient (GM-CSF +/+) control animals and GM-CSF -/- mice. Lung injury, quantitated by measuring lung myeloper-oxidase activity (an indicator of neutrophil sequestration), alveolar-capillary permeability, and alveolar membrane thickness was less severe in GM-CSF -/- than in GM-CSF +/+ mice. In GM-CSF +/+ mice, pancreas, lung and serum GM-CSF levels increase during pancreatitis. Lung levels of macrophage inflammatory protein (MIP)-2 are also increased during pancreatitis, but, in this case, the rise is less profound in GM-CSF -/- mice than in GM-CSF +/+ controls. Administration of anti-MIP-2 antibodies was found to reduce the severity of pancreatitis-associated ALI. Our findings indicate that GM-CSF plays a critical role in coupling pancreatitis to ALI and suggest that GM-CSF may act indirectly by regulating the release of other proinflammatory factors including MIP-2.

Original languageEnglish (US)
Pages (from-to)L541-L548
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume283
Issue number3 27-3
DOIs
StatePublished - Sep 2002
Externally publishedYes

Keywords

  • Adhesion molecules
  • Adult respiratory distress syndrome
  • Caerulein
  • Granulocyte-macrophage colony-stimulating factor
  • Inflammation
  • Neutrophils

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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