| First Author | Frossard JL | Year | 2002 |
| Journal | Am J Physiol Lung Cell Mol Physiol | Volume | 283 |
| Issue | 3 | Pages | L541-8 |
| PubMed ID | 12169573 | Mgi Jnum | J:108268 |
| Mgi Id | MGI:3623631 | Doi | 10.1152/ajplung.00413.2001 |
| Citation | Frossard JL, et al. (2002) In vivo evidence for the role of GM-CSF as a mediator in acute pancreatitis-associated lung injury. Am J Physiol Lung Cell Mol Physiol 283(3):L541-8 |
| abstractText | 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. |
