Fibrinogen protects neutrophils from the cytotoxic effects of histones and delays neutrophil extracellular trap formation induced by ionomycin.

Scientific Reports
Matthew LockeColin Longstaff

Abstract

Neutrophils are pivotal players in immune defence which includes a process of release of histones and DNA as neutrophil extracellular traps (NETs). Histones, while toxic to invading pathogens, also kill host cells, including neutrophils. Bacteria have evolved mechanisms to escape neutrophils, including the secretion of leucocidins (e.g. ionomycin). Live cell video microscopy showed how fibrinogen and fibrin influence NETosis and neutrophil responses to extracellular histones. Histones were rapidly lethal to neutrophils after binding to cells, but formation of fibrinogen/fibrin-histone aggregates prevented cell death. Histone cytotoxicity was also reduced by citrullination by peptidyl arginine deiminase 4, or digestion by serine proteases. Ionomycin and phorbol 12-myristate 13 acetate (PMA) are used to trigger NETosis. Fibrinogen was responsible for a second distinct mechanism of neutrophil protection after treatment with ionomycin. Fibrinogen clustered on the surface of ionomycin-stimulated neutrophils to delay NETosis; and blocking the β integrin receptor, αMβ2, abolished fibrinogen protection. Fibrinogen did not bind to or protect neutrophils stimulated with PMA. Fibrinogen is an acute phase protein that will protect exposed ...Continue Reading

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Citations

Feb 12, 2021·International Journal of Molecular Sciences·David Alexander Christian MessererMarkus Huber-Lang
Nov 2, 2020·Thrombosis and Haemostasis·Matthew Locke, Colin Longstaff
Jun 8, 2021·Neuropsychiatric Disease and Treatment·Wei ChengJian Chen
Jul 7, 2021·EJHaem·Jecko Thachil
Jul 20, 2021·Seminars in Cancer Biology·Leonardo CristinzianoMaria Rosaria Galdiero
Aug 5, 2021·Scientific Reports·Wai-Hoe LauKonstantin Pervushin
Sep 25, 2021·Journal of Thrombosis and Haemostasis : JTH·Jecko Thachil

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Methods Mentioned

BETA
PMA
flow cytometry
confocal microscopy
X-ray
protein assay

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