How anti-neutrophil cytoplasmic autoantibodies activate neutrophils

Clin Exp Immunol. 2012 Sep;169(3):220-8. doi: 10.1111/j.1365-2249.2012.04615.x.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / immunology*
  • Antibodies, Antineutrophil Cytoplasmic / immunology*
  • Antigen-Antibody Reactions
  • Antigens, Surface / immunology
  • Autoantigens / immunology
  • Cell Membrane / enzymology
  • Cell Membrane / immunology
  • Cytokines / metabolism
  • GPI-Linked Proteins / immunology
  • Humans
  • Immunoglobulin Fc Fragments / immunology
  • Intracellular Membranes / enzymology
  • Intracellular Membranes / immunology
  • Lysosomal-Associated Membrane Protein 2
  • Lysosome-Associated Membrane Glycoproteins / immunology
  • Myeloblastin / immunology
  • Neutrophil Activation / immunology*
  • Neutrophils / enzymology
  • Neutrophils / immunology*
  • Organelles / enzymology
  • Organelles / immunology
  • Peroxidase / immunology
  • Phosphatidylinositol 3-Kinases / immunology
  • Receptors, IgG / immunology
  • Signal Transduction / immunology

Substances

  • Antibodies, Antineutrophil Cytoplasmic
  • Antigens, Surface
  • Autoantigens
  • Cytokines
  • FCGR3B protein, human
  • GPI-Linked Proteins
  • Immunoglobulin Fc Fragments
  • LAMP2 protein, human
  • Lysosomal-Associated Membrane Protein 2
  • Lysosome-Associated Membrane Glycoproteins
  • Receptors, IgG
  • Peroxidase
  • Phosphatidylinositol 3-Kinases
  • Myeloblastin