title: Autophagic-like cell death in neutrophils induced by autoantibodies.
abstract: Human neutrophils undergo autophagic-like cell death following Sialic acid binding immunoglobulin-like lectin-9 (Siglec-9) ligation and concurrent stimulation with certain, but not all, neutrophil survival cytokines. Caspase inhibition by these cytokines is required, but is not sufficient, to trigger this particular form of cell death. Additional mechanisms may involve reactive oxygen species (ROS), and blocking of ROS or prevention of ROS production prevents autophagic-like neutrophil death. Interestingly, human intravenous immunoglobulin (IVIg) preparations contain natural anti-Siglec-9 autoantibodies, which are able to ligate Siglec-9 on neutrophils and induce autophagic-like cell death in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and some other survival cytokines. Here, we discuss the pathophysiological and therapeutic implications of these recent findings.
authors.affiliation: Department of Pharmacology, University of Bern, Friedbühlstrasse 49, CH-3010 Bern, Switzerland.
authors.forename: Stephan
authors.initials: S
authors.lastname: von Gunten
authors.forename: Hans-Uwe
authors.initials: HU
authors.lastname: Simon
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D017209:Apoptosis / Q000502:physiology; D001323:Autoantibodies / Q000276:immunology*; D016923:Cell Death / Q000276:immunology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000502:physiology; D006801:Humans; D037102:Lectins / Q000378:metabolism; D008954:Models, Biological; D009504:Neutrophils / Q000276:immunology*; D063265:Sialic Acid Binding Immunoglobulin-like Lectins
chemical_list: D015703:Antigens, CD; D001323:Autoantibodies; D037102:Lectins; C412227:SIGLEC9 protein, human; D063265:Sialic Acid Binding Immunoglobulin-like Lectins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor