Castells M C, Friend D S, Bunnell C A, Hu X, Kraus M, Osteen R T, Austen K F
Department of Medicine, Harvard Medical School, Boston, MA, USA.
J Allergy Clin Immunol. 1996 Oct;98(4):831-40. doi: 10.1016/s0091-6749(96)70133-1.
Systemic mastocytosis is characterized by mast cell infiltration of bone marrow and tissues in the absence of identified circulating bone marrow-derived progenitors. A 58-year-old man was first seen with aggressive systemic mastocytosis manifested by urticaria pigmentosa, hepatosplenomegaly, generalized bone lesions, anemia, thrombocytopenia, monoclonal gammopathy, and increased urine histamine levels.
A rapidly progressive anemia and thrombocytopenia dictated a splenectomy. We sought to identify the mast cell progenitors in the peripheral blood and to provide evidence of their maturation in tissues with immunohistochemical and ultrastructural analyses.
The peripheral blood contained 1% to 3% nonmetachromatic mononuclear cells with eccentric nuclei that expressed the mast cell proteases, tryptase and carboxypeptidase A, along with c-kit, stem cell factor (SCF), and high-affinity IgE receptor (Fc epsilon RI), but not chymase. Similar mononuclear cells colocalized in the spleen and lymph nodes with mature, metachromatic mast cells that expressed tryptase, chymase, carboxypeptidase A, c-kit, SCF, and Fc epsilon RI. Electron microscopy disclosed, at each site, a mature mast cell population with electron-dense, scroll-poor granules.
The peripheral blood of a patient with aggressive systemic mastocytosis contained immature mononuclear cells of the mast cell lineage that express c-kit, SCF, tryptase, carboxypeptidase A, and Fc epsilon RI. These cells were also found in the skin, spleen, and lymph nodes where they presumably expand, differentiate, and mature, assuming the mast cell phenotype for those tissues characterized by metachromasia, expression of a full range of mast cell-related secretory granule proteases, and ultrastructural appearance. The presence of SCF on the surface membrane of the circulating, highly immature mast cells suggests an autocrine regulation of the c-kit-SCF interaction.
系统性肥大细胞增多症的特征是骨髓和组织中有肥大细胞浸润，且不存在已识别的循环骨髓源性祖细胞。一名58岁男性首次就诊时表现为侵袭性系统性肥大细胞增多症，有色素性荨麻疹、肝脾肿大、全身性骨病变、贫血、血小板减少、单克隆丙种球蛋白病以及尿组胺水平升高。
快速进展的贫血和血小板减少促使进行脾切除术。我们试图通过免疫组织化学和超微结构分析来鉴定外周血中的肥大细胞祖细胞，并提供其在组织中成熟的证据。
外周血中含有1%至3%的非异染性单核细胞，其核偏位，表达肥大细胞蛋白酶、类胰蛋白酶和羧肽酶A，以及c-kit、干细胞因子（SCF）和高亲和力IgE受体（FcεRI），但不表达糜酶。类似的单核细胞与表达类胰蛋白酶、糜酶、羧肽酶A、c-kit、SCF和FcεRI的成熟异染性肥大细胞共定位在脾脏和淋巴结中。电子显微镜显示，在每个部位都有一群成熟的肥大细胞，其颗粒电子密度高且螺旋结构少。
侵袭性系统性肥大细胞增多症患者的外周血中含有肥大细胞系的未成熟单核细胞，这些细胞表达c-kit、SCF、类胰蛋白酶、羧肽酶A和FcεRI。这些细胞也存在于皮肤、脾脏和淋巴结中，在那里它们可能增殖、分化并成熟，呈现出那些以异染性、表达一系列与肥大细胞相关的分泌颗粒蛋白酶以及超微结构为特征的组织的肥大细胞表型。循环中高度未成熟的肥大细胞表面膜上存在SCF，提示c-kit-SCF相互作用存在自分泌调节。
