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Patients with acute pancreatitis complicated by organ failure show highly aberrant monocyte signaling profiles assessed by phospho-specific flow cytometry
- Source :
- Critical care medicine. 38(8)
- Publication Year :
- 2010
-
Abstract
- To outline signaling profiles and transmigration capacity of monocytes of patients with severe acute pancreatitis.Prospective study.University hospital intensive care unit.Thirteen patients with severe acute pancreatitis. All patients had organ dysfunction (acute respiratory distress syndrome in 12, renal dysfunction in eight). Healthy volunteers served as reference subjects.Blood samples were collected after admission to the intensive care unit.Phosphorylation of nuclear factor-kappaB and p38, signal transducers and activators of transcription (STATs) 1, 3, 5, and extracellular signal-regulated kinases 1/2 in appropriately stimulated and nonstimulated samples were studied using phospho-specific whole-blood flow cytometry. Monocyte chemotactic protein-1-induced transmigration of monocytes among mononuclear cells obtained by density gradient centrifugation was studied using Transwell cell culture inserts covered with confluent layer of endothelial EA-HY cells. Phosphorylation levels of nuclear factor-kappaB induced by tumor necrosis factor, bacterial lipopolysaccharide, muramyl dipeptide, Escherichia coli, Staphylococcus aureus, and Staphylococcus epidermidis were significantly lower in patients' monocytes than monocytes of healthy reference subjects, whereas mitogen-activated protein kinase p38 phosphorylation levels were normal. Phosphorylation levels induced by interleukin-6 in STAT1 and STAT3 and by combination of phorbol 12-myristate 13-acetate and calcium ionophore A23187 in extracellular signal-regulated kinases 1/2, members of a mitogen-activated protein kinase family, were depressed in patients' monocytes, whereas phosphorylation levels induced by granulocyte-macrophage colony-stimulating factor in STAT5 was normal. In nonstimulated samples, phosphorylation levels were normal. The transmigration percentage of patients' monocytes was significantly lower than that of reference monocytes.In severe acute pancreatitis, monocytes show impaired nuclear factor kappaB and STAT1 activation, which may increase susceptibility to secondary infections. p38 activation is normal and STAT3 activation is depressed, which may contribute to maintenance of systemic inflammation. Extracellular signal-regulated kinases 1/2 activation is impaired, which may depress monocytes' transmigration and may consequently increase risk of infection. Monitoring of monocyte signaling profiles may aid in finding new therapeutic approaches and predictors of outcome of severe acute pancreatitis.
- Subjects :
- Male
Pathology
Necrosis
Critical Care and Intensive Care Medicine
p38 Mitogen-Activated Protein Kinases
Monocytes
Hospitals, University
0302 clinical medicine
Reference Values
STAT5 Transcription Factor
Prospective Studies
Phosphorylation
Prospective cohort study
Extracellular Signal-Regulated MAP Kinases
0303 health sciences
medicine.diagnostic_test
Pancreatitis, Acute Necrotizing
Middle Aged
Flow Cytometry
Prognosis
3. Good health
Intensive Care Units
medicine.anatomical_structure
030220 oncology & carcinogenesis
Acute pancreatitis
medicine.symptom
Signal Transduction
Adult
medicine.medical_specialty
Critical Care
Critical Illness
Multiple Organ Failure
macromolecular substances
Risk Assessment
Sensitivity and Specificity
Statistics, Nonparametric
Flow cytometry
03 medical and health sciences
Predictive Value of Tests
Intensive care
medicine
Humans
030304 developmental biology
business.industry
Monocyte
Tumor Suppressor Proteins
Organ dysfunction
medicine.disease
Case-Control Studies
Pancreatitis
business
Biomarkers
Subjects
Details
- ISSN :
- 15300293
- Volume :
- 38
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- Critical care medicine
- Accession number :
- edsair.doi.dedup.....bd4cd4dd710ab0aef9d7c4bcc8a395cc