Interferon-gamma promotes the survival and Fc epsilon RI-mediated histamine release in cultured human mast cells.
We examined the effects of interferon-gamma (IFN-gamma) on 100% pure human mast cells generated in suspension cultures of umbilical cord blood mononuclear cells in the presence of stem cell factor (SCF) and interleukin-6 (IL-6). When mast cells were suspended in serum-free medium without any cytokine after the withdrawal of SCF and IL-6, they died over a period of 5 days because of apoptosis. IFN-gamma in the cultures suppressed apoptosis and prolonged their survival in a dose-dependent manner. This survival-promoting effect of IFN-gamma was blocked by neutralizing antibodies to IFN-gamma or to IFN-gamma receptor (IFN-gamma R). When mast cells were incubated with IFN-gamma in serum-free medium for more than 4 hr during sensitization, immunoglobulin E (IgE)/anti-IgE antibody-induced histamine release was effectively enhanced. Polymerase chain reaction (PCR) amplification of the alpha-chain of IFN-gamma R (IFN-gamma R alpha) yielded products of the correct size predicted from the sequence of the receptor. In addition, flow cytometry using anti-IFN-gamma R monoclonal antibodies (mAbs) indicated that these mast cells bear IFN-gamma R on their surface. These findings suggested that IFN-gamma activates human mast cells via specific receptors in certain aspects of inflammatory reactions.
Yanagida
M
M
Pharmaceutical Development Laboratory, Kirin Brewery Co., Ltd, Gunma, Japan.
Fukamachi
H
H
Takei
M
M
Hagiwara
T
T
Uzumaki
H
H
Tokiwa
T
T
Saito
H
H
Iikura
Y
Y
Nakahata
T
T
D000906:Antibodies / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006636:Histamine Release / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000494:pharmacology*; D015850:Interleukin-6 / Q000378:metabolism; D008407:Mast Cells / Q000187:drug effects / Q000502:physiology*; D016133:Polymerase Chain Reaction; D017455:Receptors, IgE / Q000276:immunology; D017471:Receptors, Interferon / Q000276:immunology; D019089:Stem Cell Factor / Q000378:metabolism; D013268:Stimulation, Chemical
D000906:Antibodies; D015850:Interleukin-6; D017455:Receptors, IgE; D017471:Receptors, Interferon; D019089:Stem Cell Factor; D007371:Interferon-gamma