Human and mouse mast cells use the tetraspanin CD9 as an alternate interleukin-16 receptor

• Published in: Blood 2006-01, Vol.107 (1), p.135-142
• Main Authors: Qi, Jian C., Wang, Jing, Mandadi, Sravan, Tanaka, Kumiko, Roufogalis, Basil D., Madigan, Michele C., Lai, Kenneth, Yan, Feng, Chong, Beng H., Stevens, Richard L., Krilis, Steven A.
• Format: Article
• Language: English
• Subjects: Animals; Antigens, CD - metabolism; Antigens, CD - physiology; Biological and medical sciences; Bone Marrow Cells; Calcium Signaling; Cells, Cultured; Chemotaxis; Fetal Blood; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; Immunobiology; Interleukin-16 - metabolism; Interleukin-16 - physiology; Mast Cells - cytology; Mast Cells - physiology; Membrane Glycoproteins - metabolism; Membrane Glycoproteins - physiology; Mice; Monocytes, macrophages; Myeloid cells: ontogeny, maturation, markers, receptors; Phosphatidylinositol 3-Kinases - metabolism; Signal Transduction; Tetraspanin 29
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2005-03-1312

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.