IgA enhances NETosis and release of neutrophil extracellular traps by polymorphonuclear cells via Fcα receptor I

J Immunol. 2014 Mar 1;192(5):2374-83. doi: 10.4049/jimmunol.1300261. Epub 2014 Feb 3.

Abstract

Polymorphonuclear cells (neutrophils) are the first cells that arrive at sites of infections. According to the current dogma, they are involved in eliminating bacteria, after which they die through apoptosis. We now demonstrate that enhanced IgA-induced phagocytosis of bacteria or beads by neutrophils led to increased cell death. Nuclear changes and positivity for the general cell death marker 7-aminoactinomycin D were observed, but the absence of annexin V membrane staining supported that neutrophils did not die via apoptosis, in contrast to neutrophils that had not phagocytosed bacteria. Moreover, increased release of neutrophil extracellular traps (NETs) was observed, which was most likely due to augmented production of reactive oxygen species after uptake of IgA-opsonized particles. Blocking the IgA Fc receptor FcαRI abrogated phagocytosis and NET formation. Thus, FcαRI triggering on neutrophils resulted in a rapid form of cell death that is referred to as NETosis, as it is accompanied by the release of NETs. As such, IgA may play a prominent role in mucosal inflammatory responses, where it is the most prominent Ab, because it enhanced both phagocytosis of bacteria and formation of NETs, which are effective mechanisms that neutrophils employ to eliminate pathogens.

Publication types

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

MeSH terms

  • Annexin A5 / immunology
  • Antigens, CD / immunology
  • Bacteria / immunology*
  • Cell Death / drug effects
  • Cell Death / immunology
  • Dactinomycin / analogs & derivatives
  • Dactinomycin / pharmacology
  • Female
  • Fluorescent Dyes / pharmacology
  • Humans
  • Immunity, Mucosal / physiology*
  • Immunoglobulin A / immunology*
  • Inflammation / immunology
  • Male
  • Neutrophils / immunology*
  • Phagocytosis / drug effects
  • Phagocytosis / immunology*
  • Receptors, Fc / immunology

Substances

  • Annexin A5
  • Antigens, CD
  • Fc(alpha) receptor
  • Fluorescent Dyes
  • Immunoglobulin A
  • Receptors, Fc
  • Dactinomycin
  • 7-aminoactinomycin D