title: Clustering of apoptotic cells via bystander killing by peroxides.
abstract: Clustering of apoptotic cells is a characteristic of many developing or renewing systems, suggesting that apoptotic cells kill bystanders. Bystander killing can be triggered experimentally by inducing apoptosis in single cells and may be based on the exchange of as yet unidentified chemical cell death signals between nearby cells without the need for cell-to-cell communication via gap junctions. Here we demonstrate that apoptotic cell clusters occurred spontaneously, after serum deprivation or p53 transfection in cell monolayers in vitro. Clustering was apparently induced through bystander killing by primary apoptotic cells. Catalase, a peroxide scavenger, suppressed bystander killing, suggesting that hydrogen peroxide generated by apoptotic cells is the death signal. Although p53 expression increased the number of apoptoses, clustering was found to be similar around apoptotic cells whether or not p53 was expressed, indicating that there is no specific p53 contribution to bystander killing. Bystander killing through peroxides emitted by apoptotic cells may propagate tissue injury in different pathological situations and be relevant in chemo-, gamma-ray, and gene therapy of cancer.
authors.affiliation: Experimental Alcohol and Drug Addiction Research Section, Department of Clinical Neuroscience and. Department of Medical Biochemistry and Biophysics, Karolinska Institute S-171 76, Stockholm, Sweden.
authors.forename: K
authors.initials: K
authors.lastname: Reznikov
authors.forename: L
authors.initials: L
authors.lastname: Kolesnikova
authors.forename: A
authors.initials: A
authors.lastname: Pramanik
authors.forename: K
authors.initials: K
authors.lastname: Tan-No
authors.forename: I
authors.initials: I
authors.lastname: Gileva
authors.forename: T
authors.initials: T
authors.lastname: Yakovleva
authors.forename: R
authors.initials: R
authors.lastname: Rigler
authors.forename: L
authors.initials: L
authors.lastname: Terenius
authors.forename: G
authors.initials: G
authors.lastname: Bakalkin
mesh_terms: D017209:Apoptosis / Q000502:physiology; D002374:Catalase / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004347:Drug Interactions; D006367:HeLa Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000494:pharmacology*; D013050:Spectrometry, Fluorescence; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
chemical_list: D016159:Tumor Suppressor Protein p53; D006861:Hydrogen Peroxide; D002374:Catalase