In vivo evidence for the role of GM-CSF as a mediator in acute pancreatitis-associated lung injury
2002; American Physical Society; Volume: 283; Issue: 3 Linguagem: Inglês
10.1152/ajplung.00413.2001
ISSN1522-1504
AutoresJean‐Louis Frossard, Ashok K. Saluja, Nicolas Mach, Hong Sik Lee, Lakshmi Bhagat, Antoine Hadenque, Laura Rubbia‐Brandt, Glenn Dranoff, Michael L. Steer,
Tópico(s)Congenital Diaphragmatic Hernia Studies
ResumoSevere 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 (12×) 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.
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