Kirshenbaum A S, Worobec A S, Davis T A, Goff J P, Semere T, Metcalfe D D
Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-1881, USA.
Exp Hematol. 1998 Mar;26(3):245-51.
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.
为了鉴定抑制人肥大细胞生长的细胞因子，我们在γ-干扰素（IFNγ）-1b和α-干扰素（IFNα）-2b存在的情况下培养了HMC-1细胞以及依赖重组人干细胞因子（rhSCF）的人骨髓来源肥大细胞（HBMC）。在1000 U/mL IFNγ-1b存在时，HMC-1细胞数量减少，但在1000 U/mL IFNα-2b存在时未受影响。然后将HBMC与100 ng/mL rhSCF和10 ng/mL重组人白细胞介素-3（rhIL-3）一起培养0至7天，随后在rhSCF中培养，并给予1000 U/mL IFNα-2b或1000 U/mL IFNγ-1b。在单独使用rhSCF或与IFNα-2b联合培养的情况下，直至培养8周，出现的HBMC数量实际上是相同的。在补充了IFNγ-1b的培养物中，到4至5周时，HBMC数量和颗粒异染性的发生率显著降低（p<0.001）。当从第0天开始用人骨髓与rhSCF和IFNγ-1b一起培养时，也获得了类似的结果。成熟的依赖rhSCF的HBMC在5周时也分别单独用rhSCF或与IFNγ-1b联合培养。与在rhSCF中培养的细胞相比，用rhSCF加IFNγ-1b处理的5周龄成熟HBMC培养物中肥大细胞数量减少，并且在5至8周后，剩余的肥大细胞中甲苯胺蓝和类胰蛋白酶阳性颗粒较少。对用rhSCF加IFNγ-1b处理的成熟HBMC进行的流式细胞术分析显示，c-kit和Fc(ε)RI表达增加。肥大细胞的释放能力未增加。因此，IFNγ-1b能够抑制CD34+细胞来源的肥大细胞生长，这表明该因子应被视为治疗肥大细胞增殖紊乱的候选细胞因子。
