Human and mouse mast cells use the tetraspanin CD9 as an alternate interleukin-16 receptor.
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.
Qi
Jian C
JC
Department of Medicine, University of New South Wales, Australia.
Wang
Jing
J
Mandadi
Sravan
S
Tanaka
Kumiko
K
Roufogalis
Basil D
BD
Madigan
Michele C
MC
Lai
Kenneth
K
Yan
Feng
F
Chong
Beng H
BH
Stevens
Richard L
RL
Krilis
Steven A
SA
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism / Q000502:physiology*; D001854:Bone Marrow Cells; D020013:Calcium Signaling; D002478:Cells, Cultured; D002633:Chemotaxis; D005312:Fetal Blood; D006801:Humans; D019410:Interleukin-16 / Q000378:metabolism / Q000502:physiology*; D008407:Mast Cells / Q000166:cytology / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D015398:Signal Transduction; D060245:Tetraspanin 29
D015703:Antigens, CD; C554869:CD9 protein, human; C554870:Cd9 protein, mouse; D019410:Interleukin-16; D008562:Membrane Glycoproteins; D060245:Tetraspanin 29; D019869:Phosphatidylinositol 3-Kinases