Role of Toll-like receptor 4 on pancreatic and pulmonary injury in a mice model of acute pancreatitis associated with endotoxemia
| Autor: | Antoine Hadengue, Jean-Louis Frossard, François Mach, Catherine M. Pastor, Marc Chanson, Brenda R. Kwak, Jérôme Pugin |
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| Rok vydání: | 2004 |
| Předmět: |
Lung Diseases
Lipopolysaccharides Pathology medicine.medical_specialty Pancreatic disease Receptors Cell Surface Lung injury Critical Care and Intensive Care Medicine Lung Diseases/chemically induced/etiology/metabolism Mice Amylases/blood/secretion Intensive care medicine Animals Receptors Cell Surface/metabolism Pancreas Ceruletide ddc:616 Membrane Glycoproteins ddc:618 business.industry Toll-Like Receptors Membrane Glycoproteins/metabolism medicine.disease Pancreatitis/chemically induced/complications/metabolism Caerulein Toll-Like Receptor 4 Disease Models Animal medicine.anatomical_structure Pancreatitis Amylases Acute Disease TLR4 Pancreas/enzymology Acute pancreatitis lipids (amino acids peptides and proteins) business |
| Zdroj: | Critical Care Medicine, Vol. 32, No 8 (2004) pp. 1759-63 |
| ISSN: | 0090-3493 |
| DOI: | 10.1097/01.ccm.0000133020.47243.8e |
| Popis: | Infection of pancreatic necrosis is a severe complication of acute pancreatitis. Because Toll-like receptor 4 (TLR4) has been identified as a receptor necessary to transduct the signal of bacteria-derived lipopolysaccharide into cells, we investigated the role of TLR4 on pancreatic and pulmonary injury in acute pancreatitis and acute pancreatitis associated with endotoxemia in wild-type and TLR4-deficient mice.Laboratory investigation.University laboratory.Heterozygous TLR4 mice.Mice were injected intraperitoneally with a supramaximal dose of cerulein each hour for 10 hrs. To mimic infection, additional groups of mice were injected with lipopolysaccharide in the presence or absence of cerulein injections.The severity of acute pancreatitis was assessed by serum amylase activity, pancreatic edema, acinar cell necrosis, and pancreas myeloperoxidase activity. Lung injury was quantitated by lung microvascular permeability and lung myeloperoxidase activity. Injections of cerulein induced an edematous pancreatitis that was of similar severity in wild-type and TLR4-deficient mice. Lipopolysaccharide alone had no toxic effect on pancreas and lungs and did not worsen the pancreatic injury induced by cerulein in wild-type and TRL4-deficient mice. In contrast, lipopolysaccharide worsened pancreatitis-associated lung injury, and the deficiency in TLR4 fully prevented this aggravation.TLR4 may not play a role in the pancreatitis-associated lung injury but participates in the pulmonary injury mediated by endotoxemia. |
| Databáze: | OpenAIRE |
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