Activated T lymphocytes induce degranulation and cytokine production by human mast cells following cell-to-cell contact.
Activated mast cells reside in close apposition to T cells in some inflammatory processes. In this study, we analyzed whether this close physical proximity affects human mast cell degranulation and cytokine release. Thus HMC-1 human mast cells or primary bone marrow-derived human mast cells were cocultured with activated and with resting T cells. Mast cells cocultured with activated T cells released histamine and beta-hexosaminidase and produced tumor necrosis factor alpha (TNF-alpha), an effect that peaked at 20 h. Kinetics of histamine release paralleled the formation of heterotypic aggregates. Separation of the two cell populations with a porous membrane prevented mediator release and TNF-alpha production. Addition of the PI3-kinase inhibitor, wortmannin, inhibited the heterotypic adhesion-associated degranulation but not TNF-alpha production. These data thus indicate a novel pathway through which human mast cells are activated to both release granule-associated mediators and to produce cytokines in association with heterotypic adhesion to activated human T cells.
Bhattacharyya
S P
SP
The Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-1881, USA.
Drucker
I
I
Reshef
T
T
Kirshenbaum
A S
AS
Metcalfe
D D
DD
Mekori
Y A
YA
D000730:Androstadienes / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001854:Bone Marrow Cells; D017252:CD3 Complex / Q000276:immunology / Q000502:physiology; D002448:Cell Adhesion / Q000187:drug effects; D002450:Cell Communication / Q000276:immunology*; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis*; D003594:Cytoplasmic Granules / Q000276:immunology*; D006636:Histamine Release; D006801:Humans; D007700:Kinetics; D008213:Lymphocyte Activation; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D013601:T-Lymphocytes / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D000077191:Wortmannin; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism
D000730:Androstadienes; D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D016207:Cytokines; D000081082:Phosphoinositide-3 Kinase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D001619:beta-N-Acetylhexosaminidases; D013755:Tetradecanoylphorbol Acetate; D000077191:Wortmannin