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Interleukin‐15 enhances human neutrophil phagocytosis by a Syk‐dependent mechanism: importance of the IL‐15Rα chain
Author(s) -
Ratthé Claude,
Girard Denis
Publication year - 2004
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0605298
Subject(s) - syk , phagocytosis , piceatannol , biology , microbiology and biotechnology , interleukin 15 , cytokine , tyrosine phosphorylation , proinflammatory cytokine , phosphorylation , signal transduction , interleukin , tyrosine kinase , immunology , inflammation , biochemistry , resveratrol
Interleukin‐15 (IL‐15) is a cytokine that possesses interesting, potential therapeutic properties. However, based on several parameters including activation of neutrophils, it is also recognized as a proinflammatory cytokine. The mechanisms by which IL‐15 activates human neutrophil functions are not fully understood. Although these cells express a functional IL‐15 receptor (IL‐15R) composed of IL‐15Rα, IL‐2/15Rβ (CD122), and γ c (CD132) subunits, the role of each receptor component has not been investigated in IL‐15‐induced human neutrophil responses. In the present study, fluorescein‐activated cell sorter analysis revealed that the ability of IL‐15 to enhance neutrophil phagocytosis is not a result of increased expression of IL‐15Rα, CD122, or CD132 on the neutrophil cell surface. Pretreatment of neutrophils with specific antibodies to IL‐15Rα, CD122, or CD132 was found to inhibit phagocytosis of opsonized‐sheep red blood cells by nearly 40%, 21%, and 27%, respectively. As expected, pretreatment of neutrophils with anti‐IL‐2Rα (CD25) had no effect. Pretreatment of cells with the Syk inhibitor piceatannol was found to significantly inhibit the ability of IL‐15 to enhance phagocytosis. In addition, IL‐15 was found to induce tyrosine phosphorylation of Syk that was largely inhibited by pretreating cells with piceatannol. Moreover, we found that Syk kinase is physically associated with IL‐15Rα. We conclude that IL‐15R enhances neutrophil phagocytosis by a Syk‐dependent mechanism and that the IL‐15Rα chain plays a key role in mediating this response, at least by interacting with Syk kinase.