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.