title: How anti-neutrophil cytoplasmic autoantibodies activate neutrophils.
abstract: Neutrophils are pivotal to host defence during infectious diseases. However, activated neutrophils may also cause undesired tissue damage. Ample examples include small-vessel inflammatory diseases (vasculitis) that are associated with anti-neutrophil cytoplasmic autoantibodies (ANCA) residing in the patients' plasma. In addition to being an important diagnostic tool, convincing evidence shows that ANCA are pathogenic. ANCA-neutrophil interactions induce important cellular responses that result in highly inflammatory necrotizing vascular damage. The interaction begins with ANCA binding to their target antigens on primed neutrophils, proceeds by recruiting transmembrane molecules to initiate intracellular signal transduction and culminates in activation of effector functions that ultimately mediate the tissue damage.
authors.affiliation: Nephrologie und Internistische Intensivmedizin Charité Virchow Klinikum and Experimental and Clinical Research Center, a joint co-operation between the Charité Medical Faculty and the Max-Delbrück Center for Molecular Medicine, Berlin-Buch, Berlin, Germany. kettritz@charite.de
authors.forename: R
authors.initials: R
authors.lastname: Kettritz
mesh_terms: D000818:Animals; D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000276:immunology*; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000276:immunology*; D000937:Antigen-Antibody Reactions; D000954:Antigens, Surface / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D002462:Cell Membrane / Q000201:enzymology / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D058851:GPI-Linked Proteins / Q000276:immunology; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000276:immunology; D007425:Intracellular Membranes / Q000201:enzymology / Q000276:immunology; D052119:Lysosomal-Associated Membrane Protein 2; D051907:Lysosomal Membrane Proteins / Q000276:immunology; D053146:Myeloblastin / Q000276:immunology; D018375:Neutrophil Activation / Q000276:immunology*; D009504:Neutrophils / Q000201:enzymology / Q000276:immunology*; D015388:Organelles / Q000201:enzymology / Q000276:immunology; D009195:Peroxidase / Q000276:immunology; D019869:Phosphatidylinositol 3-Kinases / Q000276:immunology; D017452:Receptors, IgG / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D000954:Antigens, Surface; D001324:Autoantigens; D016207:Cytokines; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D007141:Immunoglobulin Fc Fragments; C497811:LAMP2 protein, human; D052119:Lysosomal-Associated Membrane Protein 2; D051907:Lysosomal Membrane Proteins; D017452:Receptors, IgG; D009195:Peroxidase; D019869:Phosphatidylinositol 3-Kinases; D053146:Myeloblastin