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Differential Regulation of Adaptive and Innate Immunity activated Human Mast Cell by Osteopontin
Author(s) -
Ng Chun Wai,
Lau Hang Yung Alaster
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.941.12
Subject(s) - immunoglobulin e , osteopontin , microbiology and biotechnology , chemistry , chemokine , interleukin 33 , cytokine , mast cell , cell adhesion molecule , tumor necrosis factor alpha , immunology , antibody , biology , inflammation , interleukin
Osteopontin (OPN), a RGD‐containing protein which has been shown to enhance inflammatory responses by modulating different functions of different cell types such as macrophages, dendritic cells and natural killer cells. However, OPN has also been shown to suppress inflammatory responses and is important in the healing process. To understand more about OPN, anti‐IgE and PGN activated human mast cells developed from human CD34 + stem cells were employed to study the role of this protein in the inflammatory responses. The release of histamine and cytokines (IL‐5, IL‐8 and TNF‐α) releases as well as cell adhesion were studied by spectro‐fluorescence assay, ELISA and CyQUANT assay respectively. OPN induced adhesion of human mast cells after anti‐IgE and PGN stimulation, and the adhesion was able to inhibit anti‐IgE‐induced IL‐5, IL‐8 and TNF‐α release while only PGN‐induced IL‐5 was enhanced by OPN. To investigate the interaction between OPN and human mast cells, cyclic RGD (cRGD) and neutralizing antibodies against integrin αVβ3 and CD44 were employed. cRGD was able to inhibit both anti‐IgE and PGN‐activated adhesion and adhesion‐mediated regulation of cytokines release. While only antibody against Integrin αVβ3 was able to reverse the anti‐IgE‐induced adhesion and the inhibition of anti‐IgE‐mediated cytokines release by OPN. In conclusion, OPN suppresses anti‐IgE‐induced inflammatory response by inhibiting the synthesis of chemokine (IL‐8) and both Th1 (TNF‐α) and Th2 (IL‐5) cytokine and the interaction is through the RGD domain in OPN and integrin αVβ3 expressed on human mast cells. On the other hand, OPN enhances Th2 (IL‐5) synthesis when human mast cells are stimulated by PGN. Research Support: RGC Grant 469310