IgA enhances NETosis and release of neutrophil extracellular traps by polymorphonuclear cells via Fcα receptor I.
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.
Department of Molecular Cell Biology and Immunology, VU University Medical Center, 1081 BT Amsterdam, The Netherlands;
Esil
E
Aleyd
Miel W M
MW
van Hout
Sonja H
SH
Ganzevles
Kees A
KA
Hoeben
Vincent
V
Everts
Jantine E
JE
Bakema
Marjolein
M
van Egmond
D017304:Annexin A5 / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology; D001419:Bacteria / Q000276:immunology*; D016923:Cell Death / Q000187:drug effects / Q000276:immunology; D003609:Dactinomycin / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D005456:Fluorescent Dyes / Q000494:pharmacology; D006801:Humans; D018928:Immunity, Mucosal / Q000502:physiology*; D007070:Immunoglobulin A / Q000276:immunology*; D007249:Inflammation / Q000276:immunology; D008297:Male; D009504:Neutrophils / Q000276:immunology*; D010587:Phagocytosis / Q000187:drug effects / Q000276:immunology*; D011961:Receptors, Fc / Q000276:immunology
D017304:Annexin A5; D015703:Antigens, CD; C036832:Fc(alpha) receptor; D005456:Fluorescent Dyes; D007070:Immunoglobulin A; D011961:Receptors, Fc; D003609:Dactinomycin; C025942:7-aminoactinomycin D