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Title: Kinase activity is impaired in neutrophils of sepsis patients
Authors: Hoogendijk, Arie J.
Vught, Lonneke A. van
Wiewel, Maryse A.
Fuhler, Gwenny M.
Belkasim-Bohoudi, Hakima
Horn, Janneke
Schultz, Marcus J.
Scicluna, Brendon P.
Peppelenbosch, Maikel P.
Veer, Cornelis Van't
Vos, Alex F. de
Poll, Tom van der
Keywords: Biomarkers
Enzyme activation
Neutrophils -- Immunology
Septicemia -- Diagnosis
Issue Date: 2019
Publisher: Ferrata-Storti Foundation
Citation: Hoogendijk, A. J., van Vught, L. A., Wiewel, M. A., Fuhler, G. M., Belkasim-Bohoudi, H., Horn, J., ... & van der Poll, T. (2019). Kinase activity is impaired in neutrophils of sepsis patients. Haematologica, 104(6), e233.
Abstract: Sepsis is a complex clinical condition that arises from multiple interacting tissues and unbalanced cell-specific host response mechanisms. Neutrophils are the most abundant circulating leukocytes and form the primary line of defense against pathogens. Upon activation and subsequent extravasation, neutrophils can engage pathogens by a broad set of actions, including phagocytosis, production of reactive oxygen species, release of antimicrobial peptides and by undergoing NETosis. Kinases play an integral role in regulating and enabling intracellular signaling cascades that control these, for neutrophil function, essential processes: for example, NADPH oxygenase assembly is regulated via Raf (RAF proto-oncogene serine/threonine-protein kinase), ERK (MAPK1/3) and MEK kinases3 and the balance of P38 MAPK and ERK upstream of GRK2 (G protein-coupled receptor kinase 2) as well as PAK and PI3K/AKT activity controls neutrophil migration. However, knowledge on kinome-wide regulation of kinases in primary neutrophils during sepsis and critical illness is limited. Using a kinome profiling approach we here uncover that, relative to patients with non-infectious critical illness, sepsis patients present a suppressed neutrophil kinase activity profile.
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