title: Mechanisms underlying mouse TNF-α stimulated neutrophil derived microparticle generation.
abstract: Despite advances in understanding and treatment of sepsis, it remains a disease with high mortality. Neutrophil Derived Microparticles (NDMPs) are present during sepsis and can modulate the immune system. As TNF-α is a cytokine that predominates in the initial stages of sepsis, we evaluated whether and how TNF-α can induce NDMPs in mice. We observed that TNF-α treatment results in increased NDMP numbers. We also determined that the activation of either TNF receptor 1 (TNFr1) or TNF receptor 2 (TNFr2) resulted in increased NDMP numbers and that activation of both resulted in an additive increase. Inhibition of Caspase 8 diminishes NDMPs generated through TNFr1 activation and inhibition of NF-κB abrogates NDMPs generated through activation of both TNFr1 and TNFr2. We conclude that the early production of TNF-α during sepsis can increase NDMP numbers through activation of the Caspase 8 pathway or NF-κB.
authors.affiliation: Division of Research, Department of Surgery, University of Cincinnati, OH, USA. bjohns00@gmail.com
authors.forename: Bobby L
authors.initials: BL
authors.lastname: Johnson
authors.forename: Holly S
authors.initials: HS
authors.lastname: Goetzman
authors.forename: Priya S
authors.initials: PS
authors.lastname: Prakash
authors.forename: Charles C
authors.initials: CC
authors.lastname: Caldwell
mesh_terms: D000818:Animals; D017209:Apoptosis; D053181:Caspase 8 / Q000378:metabolism*; D004789:Enzyme Activation; D005786:Gene Expression Regulation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism*; D009504:Neutrophils / Q000166:cytology / Q000378:metabolism*; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000378:metabolism; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000378:metabolism; D018805:Sepsis / Q000378:metabolism; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D016328:NF-kappa B; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha; C505526:Casp8 protein, mouse; D053181:Caspase 8
keywords: Caspase 8; Innate immunity; NF-κB; Sepsis; TNF-α