title: In vivo-transmigrated human neutrophils are resistant to antiapoptotic stimulation.
abstract: Neutrophils respond to microbial invasion or injury by transmigration from blood to tissue. Transmigration involves cellular activation and degranulation, resulting in altered levels of surface receptors and changed responsiveness to certain stimuli. Thus, fundamental functional changes are associated with neutrophil transmigration from blood to tissue. Neutrophils isolated from peripheral blood spontaneously enter apoptosis, a process that can be accelerated or delayed by different pro- or antiapoptotic factors. How tissue neutrophils that have transmigrated in vivo regulate cell death is poorly understood. In this study, in vivo-transmigrated neutrophils (tissue neutrophils) were collected using a skin chamber technique and compared with blood neutrophils from the same donors with respect to regulation of cell death. Skin chamber fluid contained a variety of cytokines known to activate neutrophils and regulate their lifespan. Freshly prepared tissue neutrophils had elevated activity of caspase 3/7 but were fully viable; spontaneous cell death after in vitro culture was also similar between blood and tissue neutrophils. Whereas apoptosis of cultured blood neutrophils was delayed by soluble antiapoptotic factors (e.g., TLR ligands), tissue neutrophils were completely resistant to antiapoptotic stimulation, even though receptors were present and functional. In vitro transmigration of blood neutrophils into skin chamber fluid did not fully confer resistance to antiapoptotic stimulation, indicating that a block of antiapoptotic signaling occurs specifically during in vivo transmigration. We describe a novel, functional alteration that takes place during in vivo transmigration and highlights the fact that life and death of neutrophils may be regulated differently in blood and tissue.
authors.affiliation: Sahlgrenska Academy at University of Gothenburg, Guldhedsgatan 10, SE-413 46 Gothenburg, Sweden. karin.christenson@rheuma.gu.se
authors.forename: Karin
authors.initials: K
authors.lastname: Christenson
authors.forename: Lena
authors.initials: L
authors.lastname: Björkman
authors.forename: Jennie
authors.initials: J
authors.lastname: Karlsson
authors.forename: Martina
authors.initials: M
authors.lastname: Sundqvist
authors.forename: Charlotta
authors.initials: C
authors.lastname: Movitz
authors.forename: David P
authors.initials: DP
authors.lastname: Speert
authors.forename: Claes
authors.initials: C
authors.lastname: Dahlgren
authors.forename: Johan
authors.initials: J
authors.lastname: Bylund
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000276:immunology*; D051017:Apoptosis Regulatory Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D002464:Cell Migration Inhibition / Q000276:immunology; D002465:Cell Movement / Q000276:immunology*; D002470:Cell Survival / Q000276:immunology; D002478:Cells, Cultured; D015194:Diffusion Chambers, Culture; D006801:Humans; D009504:Neutrophils / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins