Time course of signaling profiles of blood leukocytes in acute pancreatitis and sepsis

• Published in: Scandinavian journal of clinical and laboratory investigation Vol. 80; no. 2; pp. 114 - 123
• Main Authors: Turunen, Antti, Kuuliala, Antti, Penttilä, Anne, Kaukonen, Kirsi-Maija, Mustonen, Harri, Pettilä, Ville, Puolakkainen, Pauli, Kylänpää, Leena, Kuuliala, Krista
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 17.02.2020
• Subjects: Adult; Aged; Case-Control Studies; Cholangiopancreatography, Endoscopic Retrograde; Female; Flow Cytometry; HLA-DR Antigens - metabolism; Humans; leukocytes; Leukocytes - metabolism; Lipopolysaccharides - pharmacology; Male; Middle Aged; Monocytes - drug effects; Monocytes - metabolism; NF-kappa B - metabolism; Pancreatitis; Pancreatitis - blood; Pancreatitis - diagnostic imaging; Phosphorylation; sepsis; Sepsis - blood; Sepsis - etiology; Signal Transduction; STAT1 Transcription Factor - metabolism; STAT3 Transcription Factor - metabolism; Time Factors; Young Adult; leukocytes; flow cytometry; signal transduction; sepsis; Pancreatitis
• ISSN: 0036-5513; 1502-7686; 1502-7686
• DOI: 10.1080/00365513.2019.1700548

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 + Ca 2+ 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.