In vivo evidence for the role of GM-CSF as a mediator in acute pancreatitis-associated lung injury
- Authors
- Frossard J.L.; Saluja A.K.; Mach N.; Lee H.S.; Bhagat L.; Hadenque A.; Rubbia-Brandt L.; Dranoff G.; Steer M.L.
- Issue Date
- 2002
- Keywords
- Adhesion molecules; Adult respiratory distress syndrome; Caerulein; Granulocyte-macrophage colony-stimulating factor; Inflammation; Neutrophils
- Citation
- American Journal of Physiology - Lung Cellular and Molecular Physiology, v.283, no.3 27-3, pp L541 - L548
- Indexed
- SCOPUS
- Journal Title
- American Journal of Physiology - Lung Cellular and Molecular Physiology
- Volume
- 283
- Number
- 3 27-3
- Start Page
- L541
- End Page
- L548
- URI
- https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/22171
- ISSN
- 1040-0605
1522-1504
- 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.
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- Appears in
Collections - 2. Clinical Science > Department of Gastroenterology and Hepatology > 1. Journal Articles
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