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Patients with acute pancreatitis complicated by organ dysfunction show abnormal peripheral blood polymorphonuclear leukocyte signaling.
MedLine Citation:
PMID:  23561969     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
BACKGROUND/OBJECTIVES: 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:
Jani Oiva; Harri Mustonen; Marja-Leena Kylänpää; Krista Kuuliala; Sanna Siitonen; Esko Kemppainen; Pauli Puolakkainen; Heikki Repo
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Publication Detail:
Type:  Journal Article     Date:  2013-02-05
Journal Detail:
Title:  Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]     Volume:  13     ISSN:  1424-3911     ISO Abbreviation:  Pancreatology     Publication Date:    2013 Mar-Apr
Date Detail:
Created Date:  2013-04-08     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100966936     Medline TA:  Pancreatology     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  118-24     Citation Subset:  IM    
Copyright Information:
Copyright © 2013 IAP and EPC. Published by Elsevier B.V. All rights reserved.
Affiliation:
Department of Surgery, Helsinki University Central Hospital, Haartmaninkatu 8, 00290 Helsinki, Finland.
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