en
Scientific article
English

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

Publication date2002-09
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 myeloperoxidase 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.

eng
Keywords
  • Acute Disease
  • Animals
  • Antibodies / pharmacology
  • Ceruletide
  • Chemokine CXCL2
  • Chemokines / immunology
  • Chemokines / metabolism
  • Granulocyte-Macrophage Colony-Stimulating Factor / genetics
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
  • Leukocyte Count
  • Lung / drug effects
  • Lung / metabolism
  • Lung / pathology
  • Lung Diseases / etiology
  • Lung Diseases / pathology
  • Lung Diseases / physiopathology
  • Mice
  • Mice, Knockout / genetics
  • Pancreas / metabolism
  • Pancreatitis / chemically induced
  • Pancreatitis / complications
  • Pancreatitis / metabolism
  • Pancreatitis / physiopathology
  • Reference Values
  • Severity of Illness Index
Citation (ISO format)
FROSSARD, Jean-Louis et al. In vivo evidence for the role of GM-CSF as a mediator in acute pancreatitis-associated lung injury. In: American journal of physiology. Lung cellular and molecular physiology, 2002, vol. 283, n° 3, p. L541–L548. doi: 10.1152/ajplung.00413.2001
Main files (1)
Article (Published version)
accessLevelRestricted
Identifiers
ISSN of the journal1040-0605
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