title: Bystander cells enhance NK cytotoxic efficiency by reducing search time.
abstract: Natural killer (NK) cells play a central role during innate immune responses by eliminating pathogen-infected or tumorigenic cells. In the microenvironment, NK cells encounter not only target cells but also other cell types including non-target bystander cells. The impact of bystander cells on NK killing efficiency is, however, still elusive. In this study we show that the presence of bystander cells, such as P815, monocytes or HUVEC, enhances NK killing efficiency. With bystander cells present, the velocity and persistence of NK cells were increased, whereas the degranulation of lytic granules remained unchanged. Bystander cell-derived H2O2was found to mediate the acceleration of NK cell migration. Using mathematical diffusion models, we confirm that local acceleration of NK cells in the vicinity of bystander cells reduces their search time to locate target cells. In addition, we found that integrin β chains (β1, β2 and β7) on NK cells are required for bystander-enhanced NK migration persistence. In conclusion, we show that acceleration of NK cell migration in the vicinity of H2O2-producing bystander cells reduces target cell search time and enhances NK killing efficiency.
authors.affiliation: Biophysics, Center for Integrative Physiology and Molecular Medicine, School of Medicine, Saarland University, 66421 Homburg, Germany.
authors.forename: Xiao
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Biophysics, Center for Integrative Physiology and Molecular Medicine, School of Medicine, Saarland University, 66421 Homburg, Germany.
authors.forename: Renping
authors.initials: R
authors.lastname: Zhao
authors.affiliation: Department of Theoretical Physics, Saarland University, 66123 Saarbrücken, Germany.
authors.forename: Karsten
authors.initials: K
authors.lastname: Schwarz
authors.affiliation: Department of Theoretical Physics, Saarland University, 66123 Saarbrücken, Germany.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Mangeat
authors.affiliation: Biophysics, Center for Integrative Physiology and Molecular Medicine, School of Medicine, Saarland University, 66421 Homburg, Germany.
authors.forename: Eva C
authors.initials: EC
authors.lastname: Schwarz
authors.affiliation: Center for Bioinformatics, Saarland University, 66041 Saarbrücken, Germany.|Institute for Biostatistics and Informatics in Medicine and Ageing Research, Rostock University Medical Center, 18057 Rostock, Germany.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Hamed
authors.affiliation: Biophysics, Center for Integrative Physiology and Molecular Medicine, School of Medicine, Saarland University, 66421 Homburg, Germany.
authors.forename: Ivan
authors.initials: I
authors.lastname: Bogeski
authors.affiliation: Center for Bioinformatics, Saarland University, 66041 Saarbrücken, Germany.
authors.forename: Volkhard
authors.initials: V
authors.lastname: Helms
authors.affiliation: Department of Theoretical Physics, Saarland University, 66123 Saarbrücken, Germany.
authors.forename: Heiko
authors.initials: H
authors.lastname: Rieger
authors.affiliation: Biophysics, Center for Integrative Physiology and Molecular Medicine, School of Medicine, Saarland University, 66421 Homburg, Germany.
authors.forename: Bin
authors.initials: B
authors.lastname: Qu
mesh_terms: D000818:Animals; D024201:Bystander Effect / Q000276:immunology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000494:pharmacology; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology*; D051379:Mice; D009000:Monocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D016877:Oxidants / Q000378:metabolism / Q000494:pharmacology; D013997:Time Factors
chemical_list: D016877:Oxidants; D006861:Hydrogen Peroxide