Human neutrophils express the interleukin-15 receptor alpha chain (IL-15Ralpha) but not the IL-9Ralpha component.
The interleukin-15 receptor (IL-15R) is composed of at least three chains, namely gammac, IL-2Rbeta, and the recently identified IL-15Ralpha, while the IL-9R complex consists of gammac and a subunit designated IL-9Ralpha. Our previous work and that of others have shown that human neutrophils express gammac and IL-2Rbeta (two components shared with IL-2R) but not IL-2Ralpha and that IL-15 is a neutrophil agonist, whereas IL-2 is not. In this study, using flow cytometry with a specific anti-human IL-15Ralpha, we show for the first time that human neutrophils express surface IL-15Ralpha. Although we previously found that IL-15 is a neutrophil agonist, our present work shows that IL-15 does not trigger superoxide production nor cell spreading onto glass. In addition, we report that human neutrophils do not respond to IL-9 with respect to the functions/responses studied, namely, superoxide production, spreading onto glass, cell shape changes, phagocytosis, RNA synthesis, and apoptosis. Further, our results show that neutrophils do not express IL-9Ralpha as assessed by flow cytometry with a specific anti-human IL-9Ralpha antibody that stains the transfected cell line BW-h9R used as positive control. Finally, our results indicate that gammac expression was not modulated and remained stable for up to 24 h when neutrophils were stimulated with all currently known "gammac users," namely, IL-2, IL-4, IL-7, IL-9, and IL-15. We conclude that human neutrophils express all IL-15R components on their surface, including IL-15Ralpha, that IL-15 activates human neutrophils (as the IL-4 neutrophil agonist) by a mechanism which does not involve upregulation of gammac cell surface expression, and that IL-9 is not a neutrophil agonist as demonstrated by the inability to modulate the tested functions/responses that correlate with lack of the IL-9R component, namely, IL-9Ralpha.
Girard
D
D
Institut National de la Recherche Scientifique-Santé(INRS-Santé), Universitédu Québec, Pointe-Claire, Quebec, H9R 1G6, Canada. Denis.Girard@INRS-Sante.Uquebec.ca
Boiani
N
N
Beaulieu
A D
AD
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D048429:Cell Size / Q000187:drug effects / Q000502:physiology; D005434:Flow Cytometry; D006801:Humans; D019409:Interleukin-15 / Q000494:pharmacology; D016906:Interleukin-9 / Q000494:pharmacology; D007378:Interleukins / Q000494:pharmacology; D046911:Macromolecular Substances; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure*; D012313:RNA / Q000096:biosynthesis / Q000378:metabolism; D051381:Rats; D018123:Receptors, Interleukin / Q000819:agonists / Q000096:biosynthesis*; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2 / Q000819:agonists / Q000096:biosynthesis*; D053651:Receptors, Interleukin-9; D012756:Sheep; D013481:Superoxides / Q000378:metabolism
C508024:IL15RA protein, human; C508045:IL9R protein, human; C508025:Il15ra protein, mouse; C508447:Il9r protein, rat; D019409:Interleukin-15; D016906:Interleukin-9; D007378:Interleukins; D046911:Macromolecular Substances; D018123:Receptors, Interleukin; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2; D053651:Receptors, Interleukin-9; D013481:Superoxides; D012313:RNA