Pancreatitis-induced Acute Lung Injury

Guice, Karen S.; Oldham, Keith T.; Johnson, Kent J.; Kunkel, Robin G.; Morganroth, Melvin L.; Ward, Peter A.

doi:10.1097/00000658-198807000-00010

Cited by 92 publications

(37 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The dose chosen was in excess of that required to stimulate a maximal rate of digestive enzyme secretion from the pancreas. Supramaximal secretagogue stimulation of the pancreas with caerulein is known to cause acute pancreatitis characterized by initial pancreatic inflammation and acinar cell necrosis (9) followed by a secondary respiratory distress syndrome associated with hypoxemia, hypercarbia, and PMN sequestration in the lung (7,8). Previous studies have suggested a role for complement, neutrophils, and TNF in this response (10).…”

Section: Resultsmentioning

confidence: 99%

“…A linkage between the cytokine (e.g., TNF-␣ ) and chemokine systems in the genesis of these syndromes may be postulated. In rodents, a model of these processes dependent on the initiation of acute pancreatitis has been well described (7,8). After overstimulation of pancreatic exocrine acinar cells with the cholecystokinin analogue caerulein, pancreatic injury occurs that is characterized by edema, leukocyte influx into the pancreas, and elevated levels of pancreatic enzymes in the serum (9).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Targeted disruption of the beta-chemokine receptor CCR1 protects against pancreatitis-associated lung injury.

Gérard¹,

Frossard²,

Bhatia³

et al. 1997

J. Clin. Invest.

206

126

View full text Add to dashboard Cite

Abstract␤ -Chemokines and their receptors mediate the trafficking and activation of a variety of leukocytes including the lymphocyte and macrophage. An array of no less than eight ␤ -chemokine receptors has been identified, four of which are capable of recognizing the chemokines MIP1 ␣ and RANTES. Genetic deletion of one of the MIP1 ␣ and RANTES receptors, CCR5, is associated with protection from infection with HIV-1 in humans, while deletion of the ligand MIP1 ␣ protects against Coxsackie virus-associated myocarditis. In this report we show that the deletion of another receptor for MIP1 ␣ and RANTES, the CCR1 receptor, is associated with protection from pulmonary inflammation secondary to acute pancreatitis in the mouse. The protection from lung injury is associated with decreased levels of TNF-␣ in a temporal sequence indicating that the activation of the CCR1 receptor is an early event in the systemic inflammatory response syndrome. (

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Targeted disruption of the beta-chemokine receptor CCR1 protects against pancreatitis-associated lung injury.

Gérard¹,

Frossard²,

Bhatia³

et al. 1997

J. Clin. Invest.

206

126

View full text Add to dashboard Cite

show abstract

“…Destruction of the bacterial cell wall in vivo releases LPS into the body fluids resulting in activation of various cellular and humoral mediators of inflammation, such as cytokines and reactive oxygen species (ROS), which may result in septic shock and multi-organ dysfunction and failure [2, 3, 4]. …”

Section: Introductionmentioning

confidence: 99%

Protective Action of Lipopolysaccharidesin Rat Caerulein-Induced Pancreatitis: Role of Nitric Oxide

Jaworek¹,

Jachimczak²,

Tomaszewska

et al. 2000

Digestion

View full text Add to dashboard Cite

Lipopolysaccharides (LPS), the component of the cell wall of gram-negative bacteria, have been implicated in the pathogenesis of acute pancreatitis, but the mechanism of their action on the pancreas has not been fully explored. The aim of this study was to investigate the effects of various doses of LPS on the integrity of intact pancreas and that involved in acute caerulein-induced pancreatitis (CIP) in the rat and to compare these effects with those of nitric oxide (NO) donor, S-nitrose-acetylpenicillamine (SNAP). The expression of constitutive NO synthase (cNOS) and inducible NO synthase (iNOS) mRNA was also examined in the isolated pancreatic acini obtained from the inflamed pancreas of rats treated with LPS. CIP was produced by subcutaneous (s.c.) infusion of caerulein (5 μg/kg·h for 5 h) to conscious rats. Bolus injections of various doses of LPS (0.1, 1, 10, 20 or 40 mg/kg) or SNAP (1.5, 3 or 6 mg/kg) were made intraperitoneally (i.p.) either alone or 30 min prior to s.c. infusion of caerulein to induce CIP. Infusion of caerulein produced acute pancreatitis confirmed by histological examination and manifested by an increase of pancreatic mass (by about 200%). Blood levels of amylase and lipase were augmented by 400 and 800% respectively, whereas the pancreatic blood flow (PBF) was decreased by 50% in rats with CIP. Injection of low doses of LPS (0.1–1 mg/kg i.p.) or SNAP (1.5–3 mg/kg i.p.) 30 min prior to caerulein infusion reversed the harmful effects of pancreatic overstimulation with caerulein and reduced significantly the histological manifestations of CIP such as edema, neutrophil infiltration and vacuolization of the acinar cells. These protective effects of low doses of LPS pretreatment on the pancreas were completely antagonized by the suppression of the activity of NO synthase (NOS) with N^G-nitro-L-arginine (L-NNA) applied (20 mg/kg i.p.) 15 min prior to the LPS injection. Combination of L-arginine (100 mg/kg i.p.), a substrate for NOS, with L-NNA given prior to low doses of LPS, restored the LPS-induced protection of the pancreas in rats with CIP. In contrast, higher doses of LPS (20–40 mg/kg i.p.) or SNAP (6 mg/kg i.p.), which produced a significant fall of the PBF, did not protect the pancreas against CIP. Administration of various doses of LPS to rats with CIP resulted in significant and dose-dependent stimulation of NO biosynthesis in the isolated acini obtained from the pancreas of these animals. LPS enhanced the expression of both cNOS and iNOS in the pancreatic acini obtained from rats subjected to CIP. The signal for cNOS mRNA was detected in all samples, reaching peak at the protective dose of LPS (1 mg/kg i.p.), while iNOS was overexpressed only at the highest doses of LPS that failed to exhibit the protective activity. We conclude that the pretreatment with low doses of LPS protects the pancreas against the damage provoked by CIP and this effect could be attributed, at least in part, to the activation of L-arginine-NO system in the pancreas.

show abstract

“…Several models of acute pancreatitis in experimental animals have been shown to be accompanied by measurable lung injury (9,14,15,37), and a number of recent studies have focused on identifying the factors that couple pancreatic inflammation to lung injury in those models (1,2,10,26). In the current communication, we have utilized the secretagogue (caerulein)-induced model of acute pancreatitis (20) in mice to examine the role played by granulocyte-macrophage colony-stimulating factor (GM-CSF) in mediating acute lung injury in this model.…”

mentioning

confidence: 99%

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

Frossard

Saluja²,

Mach

et al. 2002

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

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 (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.

show abstract

Pancreatitis-induced Acute Lung Injury

Cited by 92 publications

References 15 publications

Targeted disruption of the beta-chemokine receptor CCR1 protects against pancreatitis-associated lung injury.

Targeted disruption of the beta-chemokine receptor CCR1 protects against pancreatitis-associated lung injury.

Protective Action of Lipopolysaccharidesin Rat Caerulein-Induced Pancreatitis: Role of Nitric Oxide

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

Contact Info

Product

Resources

About