title: NET amyloidogenic backbone in human activated neutrophils.
abstract: Activated human neutrophils produce a fibrillar DNA network [neutrophil extracellular traps (NETs)] for entrapping and killing bacteria, fungi, protozoa and viruses. Our results suggest that the neutrophil extracellular traps show a resistant amyloidogenic backbone utilized for addressing reputed proteins and DNA against the non-self. The formation of amyloid fibrils in neutrophils is regulated by the imbalance of reactive oxygen species (ROS) in the cytoplasm. The intensity and source of the ROS signal is determinant for promoting stress-associated responses such as amyloidogenesis and closely related events: autophagy, exosome release, activation of the adrenocorticotrophin hormone/α-melanocyte-stimulating hormone (ACTH/α-MSH) loop and synthesis of specific cytokines. These interconnected responses in human activated neutrophils, that have been evaluated from a morphofunctional and quantitative viewpoint, represent primitive, but potent, innate defence mechanisms. In invertebrates, circulating phagocytic immune cells, when activated, show responses similar to those described previously for activated human neutrophils. Invertebrate cells within endoplasmic reticulum cisternae produce a fibrillar material which is then assembled into an amyloidogenic scaffold utilized to convey melanin close to the invader. These findings, in consideration to the critical role played by NET in the development of several pathologies, could explain the structural resistance of these scaffolds and could provide the basis for developing new diagnostic and therapeutic approaches in immunomediated diseases in which the innate branch of the immune system has a pivotal role.
authors.affiliation: Department of Biotechnology and Life Sciences, University of Insubria, Varese, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Pulze
authors.affiliation: Department of Biotechnology and Life Sciences, University of Insubria, Varese, Italy.|IRCCS MultiMedica, Scientific and Technology Park, Milano, Italy.
authors.forename: B
authors.initials: B
authors.lastname: Bassani
authors.affiliation: Department of Biotechnology and Life Sciences, University of Insubria, Varese, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Gini
authors.affiliation: Department of Biotechnology and Life Sciences, University of Insubria, Varese, Italy.
authors.forename: P
authors.initials: P
authors.lastname: D'Antona
authors.affiliation: Department of Biotechnology and Life Sciences, University of Insubria, Varese, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Grimaldi
authors.affiliation: Center of Research in Medical Pharmacology, University of Insubria, Varese, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Luini
authors.affiliation: Center of Research in Medical Pharmacology, University of Insubria, Varese, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Marino
authors.affiliation: Department of Biotechnology and Life Sciences, University of Insubria, Varese, Italy.|IRCCS MultiMedica, Scientific and Technology Park, Milano, Italy.
authors.forename: D M
authors.initials: DM
authors.lastname: Noonan
authors.affiliation: Department of Biotechnology and Life Sciences, University of Insubria, Varese, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Tettamanti
authors.affiliation: Department of Biotechnology and Life Sciences, University of Insubria, Varese, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Valvassori
authors.affiliation: Department of Biotechnology and Life Sciences, University of Insubria, Varese, Italy.
authors.forename: M
authors.initials: M
authors.lastname: de Eguileor
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000502:physiology; D000682:Amyloid / Q000378:metabolism*; D000818:Animals; D001343:Autophagy; D055354:Exosomes / Q000502:physiology; D065206:Extracellular Traps / Q000276:immunology* / Q000502:physiology*; D006801:Humans; D007113:Immunity, Innate; D018375:Neutrophil Activation; D009504:Neutrophils / Q000276:immunology* / Q000648:ultrastructure; D017382:Reactive Oxygen Species; D000521:alpha-MSH / Q000378:metabolism
chemical_list: D000682:Amyloid; D017382:Reactive Oxygen Species; D000521:alpha-MSH; D000324:Adrenocorticotropic Hormone
keywords: ACTH axis; ROS evaluation; amyloidogenesis; exosomes; neutrophil extracellular trap