title: Neutrophil cell death in response to infection and its relation to coagulation.
abstract: Neutrophil is a major player in the pathophysiology of severe sepsis. Recent studies have revealed that the cell death mechanism of neutrophils directly relates to the development of organ dysfunction during sepsis. Here we discuss about the different types of neutrophil cell death such as necrosis, apoptosis, autophagy, and the unique cell death style dubbed NETosis. NETosis cells release neutrophil extracellular traps (NETs), which are composed of chromatin bound to granular and nucleic proteins. The primary purpose of NET release is thought to be the control of microbial infections; however, it acts as a danger signal for the host as well. The harmful substances such as DNA, histones, and high-mobility group box 1 (HMGB1) and many other danger-associated molecular patterns (DAMPs) released along with NETosis or from necrotic neutrophils also contribute to the pathogenesis of sepsis. At the same time, the coagulation system, which is closely tied to these neutrophil cell death mechanisms, is often over-activated. It is well known that individual bacterial pathogens express virulence factors that modulate cell death pathways and influence the coagulation disorder during sepsis. Moreover, extensive cross talk exists between these two phenomena, whereby inflammation leads to activation of coagulation and coagulation considerably affects inflammatory activity. A greater knowledge of cell death pathways in sepsis informs the potential for future therapies designed to ameliorate excessive immune responses during sepsis.
authors.affiliation: Department of Emergency and Disaster Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421 Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Iba
authors.affiliation: Department of Emergency and Disaster Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421 Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Hashiguchi
authors.affiliation: Department of Defense and Biochemical Research, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421 Japan.
authors.forename: Isao
authors.initials: I
authors.lastname: Nagaoka
authors.affiliation: Department of Clinical Laboratory Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421 Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Tabe
authors.affiliation: Department of Emergency and Disaster Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421 Japan.
authors.forename: Miwa
authors.initials: M
authors.lastname: Murai
keywords: Apoptosis; NETosis; Necrosis; Neutrophil extracellular traps