title: Patients with acute pancreatitis complicated by organ dysfunction show abnormal peripheral blood polymorphonuclear leukocyte signaling.
abstract: OBJECTIVE
  Circulating polymorphonuclear leukocytes (PMNLs) may contribute to development of organ dysfunction in acute pancreatitis (AP). We outlined aberrations in PMNL signaling profiles in patients with AP complicated by organ dysfunction and immune suppression.
  
  
  METHODS
  Study comprised 13 patients treated at intensive care unit due to severe AP complicated by vital organ dysfunction. Mean proportion (SEM) of HLA-DR-positive monocytes was 55.0% (4.1%). 13 healthy volunteers served as reference subjects. Phosphorylation of PMNL NFκB, p38, ERK1/2 and STAT3, -5 and -6 was determined using whole blood flow cytometry. Transmigration of PMNLs was studied using endothelial EA-HY cell monolayer.
  
  
  RESULTS
  Proportions of NFκB phosphorylation-positive PMNLs were lower in the patients' than in reference subjects' blood samples supplemented with tumor necrosis factor. p38 phosphorylation was normal while ERK1/2 phosphorylation was decreased. STAT3 was constitutively activated in five patients. Proportion of patients' pSTAT6-positive cells was normal while fluorescence intensity was decreased. STAT5 phosphorylation was normal. Transmigration of patients' PMNLs was increased.
  
  
  CONCLUSIONS
  In patients with AP complicated by organ dysfunction proportion of pNFκB-positive PMNLs is decreased. This impairs patients' defense mechanisms against infection. Despite immune suppression, PMNL transmigration was increased and p38 phosphorylation capacity was not depressed, which may contribute to end organ inflammation and dysfunction.
authors.affiliation: Department of Surgery, Helsinki University Central Hospital, Haartmaninkatu 8, 00290 Helsinki, Finland.
authors.forename: Jani
authors.initials: J
authors.lastname: Oiva
authors.forename: Harri
authors.initials: H
authors.lastname: Mustonen
authors.forename: Marja-Leena
authors.initials: ML
authors.lastname: Kylänpää
authors.forename: Krista
authors.initials: K
authors.lastname: Kuuliala
authors.forename: Sanna
authors.initials: S
authors.lastname: Siitonen
authors.forename: Esko
authors.initials: E
authors.lastname: Kemppainen
authors.forename: Pauli
authors.initials: P
authors.lastname: Puolakkainen
authors.forename: Heikki
authors.initials: H
authors.lastname: Repo
mesh_terms: D000328:Adult; D000368:Aged; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009504:Neutrophils / Q000502:physiology*; D010195:Pancreatitis / Q000150:complications* / Q000473:pathology*; D010766:Phosphorylation; D050791:STAT Transcription Factors / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D016328:NF-kappa B; D050791:STAT Transcription Factors; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases