Sur Runa, Cavender Druie, Malaviya Ravi
Johnson & Johnson Pharmaceutical Research and Development, Raritan, NJ, USA.
Int Immunopharmacol. 2007 May;7(5):555-67. doi: 10.1016/j.intimp.2007.01.009. Epub 2007 Feb 14.
Mast cells have long been known to play a detrimental role in the pathogenesis of IgE-associated allergic disorders by their ability to release a wide variety of pro-inflammatory mediators. A number of studies, however, have demonstrated that mast cells play a beneficial role in innate host defense against bacterial infections. Since mast cells clearly play both physiological and pathophysiological functions in the body, it is important to learn about the components of mast cells that drive these responses. The functional roles of mast cell in vivo have been principally characterized by comparing the biological responses in mast cell-deficient mice (WBB6F(1)-W/W(v)), their normal wild-type littermates (WBB6F(1)-+/+) and mast cell deficient mice reconstituted locally or systemically with mast cells cultured from the bone marrow cells of WBB6F(1)-+/+ mice (WBB6F(1)-W/W(v)+MC). Recently investigators have demonstrated that mast cell-deficient mice (WBB6F(1)-W/W(v)) can be reconstituted with mast cells derived in vitro from the bone marrow cells of certain gene knock-out mice or genetically-manipulated embryonic stem cells. This novel approach of analyzing the biological consequences of gene mutations in mast cells will help us to better understand the role of individual gene products in mast cell responses. In this review, we discuss these new approaches to investigate the functions of mast cells in vivo.
长期以来,人们已知肥大细胞通过释放多种促炎介质,在IgE相关过敏性疾病的发病机制中发挥有害作用。然而,多项研究表明,肥大细胞在机体抵御细菌感染的天然宿主防御中发挥有益作用。由于肥大细胞在体内显然发挥着生理和病理生理功能,了解驱动这些反应的肥大细胞成分非常重要。肥大细胞在体内的功能作用主要通过比较肥大细胞缺陷小鼠(WBB6F(1)-W/W(v))、其正常野生型同窝小鼠(WBB6F(1)-+/+)以及用从WBB6F(1)-+/+小鼠骨髓细胞培养的肥大细胞进行局部或全身重建的肥大细胞缺陷小鼠(WBB6F(1)-W/W(v)+MC)的生物学反应来表征。最近,研究人员证明,肥大细胞缺陷小鼠(WBB6F(1)-W/W(v))可以用从某些基因敲除小鼠的骨髓细胞或基因操作的胚胎干细胞体外衍生的肥大细胞进行重建。这种分析肥大细胞基因突变生物学后果的新方法将有助于我们更好地理解单个基因产物在肥大细胞反应中的作用。在这篇综述中,我们讨论了这些研究肥大细胞体内功能的新方法。