Thompson H L, Metcalfe D D, Kinet J P
Mast Cell Physiology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892.
J Clin Invest. 1990 Apr;85(4):1227-33. doi: 10.1172/JCI114557.
Immediate hypersensitivity is due to the release of mediators from mast cells and basophils after the crosslinking of Fc epsilon RI. The appearance of such receptors was examined during differentiation of human and mouse bone marrow cells cultured in the presence of IL-3. As already reported, mouse bone marrow yield cultures of greater than 95% mast cells by 3 wk, whereas human bone marrow develop into cultures comprising 25% basophils by 3 wk. Here we show that transcripts for Fc epsilon RI subunits and membrane-associated receptors are apparent by 1 wk in both human and murine IL-3-dependent bone marrow cells. These cells contain few, if any, granules. The expression of transcripts and the number of receptor-positive cells continue to increase over 3 wk of culture. In parallel, a progressively larger number of cells become increasingly granulated to finally resemble either basophils or mast cells. Mature peripheral human basophils also contain transcripts for Fc epsilon RI and, therefore, may have the potential to synthesize de novo receptors. The early appearance of Fc epsilon FI during cell differentiation may be important for these cells to respond to IgE-mediated stimuli before granulation. The physiologic role of Fc epsilon RI could be to mediate lymphokine production (IL-3, IL-4, IL-6, and granulocyte/macrophage colony-stimulating factor) without inducing cellular degranulation.
速发型超敏反应是由于FcεRI交联后肥大细胞和嗜碱性粒细胞释放介质所致。在白细胞介素-3存在的情况下培养人及小鼠骨髓细胞的分化过程中,检测了此类受体的出现情况。如已报道的那样,小鼠骨髓培养3周后产生的培养物中肥大细胞含量超过95%,而人骨髓培养3周后发育为含有25%嗜碱性粒细胞的培养物。在此我们表明,在人及小鼠白细胞介素-3依赖的骨髓细胞中,1周时FcεRI亚基和膜相关受体的转录本就很明显。这些细胞几乎没有颗粒。转录本的表达和受体阳性细胞的数量在培养3周期间持续增加。与此同时,越来越多的细胞颗粒化程度逐渐增加,最终类似于嗜碱性粒细胞或肥大细胞。成熟的外周血人嗜碱性粒细胞也含有FcεRI的转录本,因此可能有能力重新合成受体。FcεRI在细胞分化过程中的早期出现可能对这些细胞在颗粒化之前对IgE介导的刺激作出反应很重要。FcεRI的生理作用可能是介导淋巴因子的产生(白细胞介素-3、白细胞介素-4、白细胞介素-6和粒细胞/巨噬细胞集落刺激因子)而不诱导细胞脱颗粒。