IL-21 enhances phagocytosis in mononuclear phagocyte cells: identification of spleen tyrosine kinase as a novel molecular target of IL-21.
J Immunol
; 190(6): 2904-12, 2013 Mar 15.
Article
em En
| MEDLINE
| ID: mdl-23396946
ABSTRACT
The biological significance of the IL-21/IL-21R system in human monocytes/macrophages is not well documented, and the expression of IL-21R is unclear and has been disputed. In this study, we showed for the first time, to our knowledge, that human monocyte-like THP-1 cells expressed the two IL-21R components, CD132 (γc) and IL-21Rα, on their cell surface, as assessed by flow cytometry. Moreover, IL-21 was found to enhance FcR-mediated phagocytosis, but not endocytosis. The ability of IL-21 to enhance phagocytosis was not associated with an increased expression of both IL-21R components at the cell surface, and IL-21 did not act in synergy with IL-15. IL-21 activated spleen tyrosine kinase (Syk), as evidenced by its ability to increase Syk phosphorylation. Using a pharmacological approach to inhibit Syk activity, and an antisense technique to downregulate Syk protein expression, we demonstrated the importance of Syk in IL-21-induced phagocytosis. In addition, both CD132 and IL-21Rα were expressed on the cell surface of naive monocytes, as well as in GM-CSF-monocyte-derived macrophages. Moreover, IL-21 also induced phagocytosis in these cells. We conclude that IL-21 possesses important biological effects in mononuclear phagocyte cells and that Syk is a novel molecular target of IL-21 that was previously unknown. Therefore, future development of therapeutic strategies targeting the IL-21/IL-21R system should consider that monocyte and macrophage cell physiology may be affected by this system.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fagócitos
/
Fagocitose
/
Proteínas Tirosina Quinases
/
Regulação para Cima
/
Interleucinas
/
Peptídeos e Proteínas de Sinalização Intracelular
Tipo de estudo:
Diagnostic_studies
Limite:
Humans
Idioma:
En
Revista:
J Immunol
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Canadá