Time course of signaling profiles of blood leukocytes in acute pancreatitis and sepsis.
Scand J Clin Lab Invest
; 80(2): 114-123, 2020.
Article
em En
| MEDLINE
| ID: mdl-31833422
ABSTRACT
Activation of intracellular signaling pathways in circulating leukocytes represents an early step in systemic immune-inflammatory response occurring e.g. in acute pancreatitis (AP) and sepsis. Previously, we found aberrations in the phosphorylation of leukocyte signaling proteins in patients with sepsis or AP (measured <48 h from hospital admission) resembling each other and associating with AP severity. Of these patients, those with sepsis or severe AP complicated by persistent organ dysfunction (OD+, n = 17) and patients with moderately severe AP (OD-, n = 6) were followed up in this study by measuring the phosphorylations at two additional time points (2-4 and 5-8 days after the initial sample) using phosphospecific whole blood flow cytometry. Twenty-eighty healthy subjects served as controls (HC). Constitutive STAT3 phosphorylation (pSTAT3) declined in monocytes and neutrophils of OD-/OD + and in lymphocytes of OD + and remained higher in OD- than HC. Monocytes of OD-/OD + showed low pSTAT3 and pSTAT1 levels in response to IL-6 through follow-up. Monocyte pNF-κB levels in response to TNF, LPS and E. coli in OD+, to E. coli in OD-, and lymphocyte pNF-κB levels in response to TNF in OD- increased during follow-up but remained lower than in HC, and neutrophil pNF-κB levels in response to TNF declined in OD-. Phorbol myristate acetate + Ca2+ ionophore-stimulated pERK1/2 decreased in neutrophils of OD-/OD+. To conclude, in patients with moderately severe or severe AP or sepsis, improvement and molecular events contributing to OD can be assessed at the level of blood leukocyte signaling.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Pancreatite
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NF-kappa B
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Sepse
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Fator de Transcrição STAT3
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Leucócitos
Tipo de estudo:
Etiology_studies
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Observational_studies
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Risk_factors_studies
Limite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article