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Inhibition of human mast cell growth and differentiation by interferon gamma-1b
A S Kirshenbaum1, A S Worobec, T A Davis
1Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-1881, USA.
Insights
Interferon gamma (IFNgamma)-1b effectively inhibits human mast cell growth and proliferation. This cytokine suppressed mast cell numbers and maturation, suggesting its potential for treating mast cell proliferation disorders.
Area of Science:
- Immunology
- Cell Biology
- Hematology
Background:
- Mast cells play crucial roles in allergic responses and inflammatory conditions.
- Dysregulation of mast cell proliferation can lead to various pathological disorders.
- Identifying inhibitory cytokines is essential for therapeutic development.
Purpose of the Study:
- To investigate the inhibitory effects of interferon gamma (IFNgamma)-1b and interferon alpha (IFNalpha)-2b on human mast cell growth.
- To evaluate the impact of these cytokines on mast cell maturation and function.
Main Methods:
- Culturing of HMC-1 cells and human bone marrow-derived mast cells (HBMCs).
- Treatment with recombinant human stem cell factor (rhSCF), recombinant human IL-3 (rhIL-3), IFNgamma-1b, and IFNalpha-2b.
- Assessment of cell numbers, granular metachromasia, and surface marker expression (c-kit, Fc(epsilon)RI) via FACS analysis.
Main Results:
- IFNgamma-1b significantly decreased HMC-1 and HBMC numbers and reduced granular metachromasia.
- IFNalpha-2b did not affect HMC-1 or HBMC numbers.
- IFNgamma-1b treatment led to decreased mast cell numbers and fewer granules in mature HBMCs, with increased c-kit and Fc(epsilon)RI expression.
- Mast cell releasability was not enhanced by IFNgamma-1b.
Conclusions:
- IFNgamma-1b demonstrates potent inhibitory effects on human mast cell proliferation from CD34+ cells.
- IFNgamma-1b suppresses mast cell growth and maturation.
- IFNgamma-1b is a potential candidate cytokine for treating disorders characterized by mast cell proliferation.
Abstract:
In an effort to identify cytokines that inhibit human mast cell growth, we cultured HMC-1 cells and recombinant human stem cell factor (rhSCF)-dependent human bone marrow-derived mast cells (HBMCs) in the presence of interferon gamma (IFNgamma)-1b and interferon alpha (IFNalpha)-2b. HMC-1 cell numbers decreased in the presence of 1000 U/mL IFNgamma-1b but were unaffected by 1000 U/mL of IFNalpha-2b. HBMCs were then cultured for 0 to 7 days with 100 ng/mL rhSCF and 10 ng/mL recombinant human IL-3 (rhIL-3), followed by culture in rhSCF and administration of either 1000 U/mL IFNalpha-2b or 1000 U/mL IFNgamma-1b. HBMCs appearing in cultures with rhSCF alone or in combination with IFNalpha-2b were virtually identical in number through 8 weeks of culture. In cultures supplemented with IFNgamma-1b, HBMCs significantly decreased in number and incidence of granular metachromasia by 4 to 5 weeks (p<0.001). Similar results were obtained when human marrow was cultured from day 0 with rhSCF and IFNgamma-1b. Mature rhSCF-dependent HBMCs were also cultured at 5 weeks with rhSCF alone or in combination with IFNgamma-1b. Compared with cells cultured in rhSCF, mature 5-week HBMC cultures treated with rhSCF plus IFNgamma-1b revealed a decrease in mast cells, and those mast cells that remained had fewer toluidine blue- and tryptase-positive granules after 5 to 8 weeks. FACS analysis of rhSCF plus IFNgamma-1b-treated mature HBMCs revealed increased c-kit and Fc(epsilon)RI expression. Mast cell releasibility was not increased. IFNgamma-lb was thus able to suppress mast cell growth from CD34+ cells, suggesting that this agent should be considered as a candidate cytokine for the treatment of disorders of mast cell proliferation.
