Interleukin-9 enhances interleukin-5 receptor expression, differentiation, and survival of human eosinophils.
Interleukin-9 (IL-9) has been implicated in the pathogenesis of allergic disorders. To examine the interaction between IL-9 and eosinophils, we evaluated mature peripheral blood eosinophils for their expression of the specific alpha-subunit of the IL-9 receptor (IL-9R-alpha). The expression of IL-9R-alpha by human eosinophils was detected at the messenger RNA (mRNA) and protein levels by reverse transcriptase-polymerase chain reaction (RT-PCR), flow cytometry, and immunocytochemical analysis, respectively. Functional analyses demonstrated that recombinant human (rh)IL-9 inhibited in vitro peripheral blood human eosinophil apoptosis in a concentration-dependent manner. We then examined the role of IL-9 in eosinophil differentiation using the human cord blood CD34(+) cells and human promyelocytic leukemia cells (HL-60). The addition of IL-9 to CD34(+) cells cultured in IL-3 and IL-5 enhanced eosinophil development, and IL-9 alone induced the expression of IL-5R-alpha. IL-9 also up-regulated the IL-5R-alpha chain cell surface expression during terminal eosinophil differentiation of the HL-60 cell line. Our findings suggest that IL-9 may potentiate in vivo eosinophil function by increasing their survival and IL-5-mediated differentiation and maturation. Taken together, these results suggest a mechanism by which IL-9 potentiates airway and tissue eosinophilia.
Gounni
A S
AS
Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada.
Gregory
B
B
Nutku
E
E
Aris
F
F
Latifa
K
K
Minshall
E
E
North
J
J
Tavernier
J
J
Levit
R
R
Nicolaides
N
N
Robinson
D
D
Hamid
Q
Q
D018952:Antigens, CD34; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004804:Eosinophils / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018922:HL-60 Cells; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006801:Humans; D016906:Interleukin-9 / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D018123:Receptors, Interleukin / Q000096:biosynthesis*; D053649:Receptors, Interleukin-5
D018952:Antigens, CD34; D016906:Interleukin-9; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D053649:Receptors, Interleukin-5