Increased secretion of TNF-alpha by costimulation of mast cells via CD28 and Fc epsilon RI.
The present study unequivocally demonstrated the expression of CD28 on murine bone marrow-derived cultured mast cells and a mast cell line, MCP-5. Stimulation of surface CD28 molecules on mast cells with anti-CD28 mAbs induced tyrosine phosphorylation of cellular proteins, including several protein tyrosine kinases and their substrates, such as Itk/Emt (Emt), Btk, Syk, c-Cbl, Shc, and Vav. CD28-stimulated tyrosine phosphorylation was followed by a rebound hypophosphorylation. Interestingly, CD28 stimulation alone elicited a low level secretion of TNF-alpha. On the other hand, cross-linking of the high affinity IgE receptor (Fc epsilon RI) on mast cells induces a set of activation events, i.e., degranulation, secretion of eicosanoids, secretion of cytokines, and DNA synthesis. Concurrent stimulation of mast cells through CD28 enhanced Fc epsilon RI-induced TNF-alpha secretion in a dose-dependent manner. Together, the present data suggest a role for CD28-mediated costimulation of mast cells in the initiation and progression of allergic responses and other diseases.
Tashiro
M
M
La Jolla Institute for Allergy and Immunology, Division of Immunobiology, San Diego, CA 92121, USA.
Kawakami
Y
Y
Abe
R
R
Han
W
W
Hata
D
D
Sugie
K
K
Yao
L
L
Kawakami
T
T
D000077329:Agammaglobulinaemia Tyrosine Kinase; D000818:Animals; D001854:Bone Marrow Cells; D018106:CD28 Antigens / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D002460:Cell Line; D003432:Cross-Linking Reagents; D004789:Enzyme Activation / Q000276:immunology; D004792:Enzyme Precursors / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D008407:Mast Cells / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D017455:Receptors, IgE / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology; D000072377:Syk Kinase; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D018106:CD28 Antigens; D003432:Cross-Linking Reagents; D004792:Enzyme Precursors; D047908:Intracellular Signaling Peptides and Proteins; D017455:Receptors, IgE; D014409:Tumor Necrosis Factor-alpha; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; D000072377:Syk Kinase; C000606897:Syk protein, mouse; C080813:emt protein-tyrosine kinase