Human NK Cells induce neutrophil apoptosis via an NKp46- and Fas-dependent mechanism.
Polymorphonuclear neutrophils (PMN) are potent inflammatory effector cells essential to host defense, but at the same time they may cause significant tissue damage. Thus, timely induction of neutrophil apoptosis is crucial to avoid tissue damage and induce resolution of inflammation. NK cells have been reported to influence innate and adaptive immune responses by multiple mechanisms including cytotoxicity against other immune cells. In this study, we analyzed the effect of the interaction between NK cells and neutrophils. Coculture experiments revealed that human NK cells could trigger caspase-dependent neutrophil apoptosis in vitro. This event was dependent on cell-cell contact, and experiments using blocking Abs indicated that the effect was mediated by the activating NK cell receptor NKp46 and the Fas pathway. CD56-depleted lymphocytes had minimal effects on neutrophil survival, suggesting that the ability to induce neutrophil apoptosis is specific to NK cells. Our findings provide evidence that NK cells may accelerate neutrophil apoptosis, and that this interaction may be involved in the resolution of acute inflammation.
Dipartimento di Medicina Sperimentale, Università di Genova, 16132 Genova, Italy.
Fredrik B
FB
Thorén
Rebecca E
RE
Riise
Jenny
J
Ousbäck
Mariella
M
Della Chiesa
Mikael
M
Alsterholm
Emanuela
E
Marcenaro
Silvia
S
Pesce
Carola
C
Prato
Claudia
C
Cantoni
Johan
J
Bylund
Lorenzo
L
Moretta
Alessandro
A
Moretta
D017209:Apoptosis; D053181:Caspase 8 / Q000378:metabolism; D002450:Cell Communication; D002478:Cells, Cultured; D018920:Coculture Techniques; D003602:Cytotoxicity, Immunologic; D053222:Fas Ligand Protein / Q000378:metabolism*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D055627:Natural Cytotoxicity Triggering Receptor 1 / Q000378:metabolism*; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction; D019014:fas Receptor / Q000378:metabolism
C491901:FAS protein, human; D053222:Fas Ligand Protein; C112260:NCR1 protein, human; D055627:Natural Cytotoxicity Triggering Receptor 1; D019014:fas Receptor; D053181:Caspase 8