1. Human and mouse mast cells use the tetraspanin CD9 as an alternate interleukin-16 receptor
- Author
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Jing Wang, Kenneth Lai, Basil D. Roufogalis, Feng Yan, Sravan Mandadi, Richard L. Stevens, Kumiko Tanaka, Steven A. Krilis, Beng H. Chong, Jian C. Qi, and Michele C. Madigan
- Subjects
medicine.medical_treatment ,Immunology ,Bone Marrow Cells ,Biology ,Biochemistry ,Tetraspanin 29 ,Wortmannin ,Mice ,Phosphatidylinositol 3-Kinases ,chemistry.chemical_compound ,Tetraspanin ,Antigens, CD ,medicine ,Animals ,Humans ,Calcium Signaling ,Mast Cells ,Cells, Cultured ,Immunobiology ,Interleukin-16 ,Membrane Glycoproteins ,Chemotaxis ,Cell Biology ,Hematology ,Fetal Blood ,medicine.disease ,Mast cell ,Molecular biology ,Cell biology ,Cytokine ,medicine.anatomical_structure ,chemistry ,Cell culture ,embryonic structures ,Mast cell sarcoma ,Signal transduction ,Signal Transduction - Abstract
Interleukin-16 (IL-16) induces the chemotaxis and activation of mast cells (MCs) and other cell types. While it has been concluded that CD4 is the primary IL-16 receptor on T cells, at least one other IL-16 receptor exists. We now show that the IL-16–responsive human MC line HMC-1 lacks CD4, and that the IL-16–mediated chemotactic and Ca2+ mobilization responses of this cell can be blocked by anti-CD9 monoclonal antibodies (mAbs) but not by mAbs directed against CD4 or other tetraspanins. Anti-CD9 mAbs also inhibited the IL-16–mediated activation of nontransformed human cord blood–derived MCs and mouse bone marrow–derived MCs by 50% to 60%. The chemotactic response of HMC-1 cells to IL-16, as well as the binding of the cytokine to the cell's plasma membrane, was inhibited by CD9-specific antisense oligonucleotides. CD9 is therefore essential for the IL-16–mediated chemotaxis and activation of the HMC-1 cell line. In support of this conclusion, IL-16 bound to CD9-expressing CHO cell transfectants. The ability of wortmannin and xestopongin C to inhibit the IL-16–mediated chemotactic response of these cells suggests that the cytokine activates a phosphatidylinositol 3-kinase (PI3K)/inositol trisphosphate–dependent signaling pathway in MCs. This is the first report of a tetraspanin that plays a prominent role in a cytokine-mediated chemotactic response of human MCs.
- Published
- 2005