Agis H, Willheim M, Sperr W R, Wilfing A, Krömer E, Kabrna E, Spanblöchl E, Strobl H, Geissler K, Spittler A, Boltz-Nitulescu G, Majdic O, Lechner K, Valent P
Department of Internal Medicine I, University of Vienna, Austria.
J Immunol. 1993 Oct 15;151(8):4221-7.
Mast cells (MC3) belong to the hemopoietic system and arise from hemopoietic precursor cells. Human MC progenitors can be detected in the bone marrow as well as in the peripheral blood (pb) and are responsive to the mast cell growth factor SCF, the ligand of the c-kit tyrosine kinase receptor. However, little is known about the subsets of cells that become committed to and differentiate into mature human MC. In this study, the identity of the circulating MC progenitor, previously felt to be a monocyte (Mo) or basophil (Ba), was investigated. For this purpose, CD14+ pb monocytes, CD17+ pb basophils and CD34+ cord blood cells were purified to homogeneity (> 95%) from mononuclear cells (normal adult donors, n = 17, cord blood, n = 2) by counter-flow centrifugation followed by cell sorting with mAb. In the presence of rhSCF, MC developed in long term suspension culture from pure CD34+ cells but not from pure Mo, pure Ba, or Ly (MC-tryptase levels on day 42: CD14+ Mo: 3.7 +/- 0.8 vs CD17+ Ba: 3.2 +/- 0.5 vs Ly: 2.0 +/- 1.5 vs control: 196.5 +/- 92.5 ng/ml, p < 0.001). Depletion of CD34+ cells from MNC resulted in a loss of MC in long term suspension culture, whereas depletion of either Mo, Ba, or Ly did not. In methyl-cellulose cultures in the presence of rhSCF, MC and tryptase could be detected in pure (CFU-mast) and mixed (CFU-myeloid/mast) MC colonies. Together, MC do not originate from circulating Mo, Ba, or Ly. The circulating MC progenitor is a CD34+, c-kit+, Ly-, CD14-, CD17- colony-forming cell. This is the first definitive demonstration that mast cells are replenished directly from early hemopoietic progenitors and thus form a unique cell lineage within the hemopoietic system.
肥大细胞（MC3）属于造血系统，起源于造血前体细胞。人类肥大细胞祖细胞可在骨髓以及外周血（pb）中检测到，并且对肥大细胞生长因子SCF（c-kit酪氨酸激酶受体的配体）有反应。然而，对于那些定向分化为成熟人类肥大细胞的细胞亚群了解甚少。在本研究中，对先前被认为是单核细胞（Mo）或嗜碱性粒细胞（Ba）的循环肥大细胞祖细胞的身份进行了研究。为此，通过逆流离心随后用单克隆抗体进行细胞分选，从单核细胞（正常成年供体，n = 17，脐血，n = 2）中纯化出均一性> 95%的CD14 + pb单核细胞、CD17 + pb嗜碱性粒细胞和CD34 +脐血细胞。在重组人干细胞因子（rhSCF）存在的情况下，纯CD34 +细胞在长期悬浮培养中可发育为肥大细胞，而纯Mo、纯Ba或Ly则不能（第42天肥大细胞糜蛋白酶水平：CD14 + Mo：3.7±0.8 vs CD17 + Ba：3.2±0.5 vs Ly：2.0±1.5 vs对照：196.5±92.5 ng/ml，p < 0.001）。从单核细胞中去除CD34 +细胞会导致长期悬浮培养中肥大细胞数量减少，而去除Mo、Ba或Ly则不会。在rhSCF存在的甲基纤维素培养中，在纯（CFU-肥大细胞）和混合（CFU-髓系/肥大细胞）肥大细胞集落中可检测到肥大细胞和糜蛋白酶。总之，肥大细胞并非起源于循环中的Mo、Ba或Ly。循环肥大细胞祖细胞是一种CD34 +、c-kit +、Ly -、CD14 -、CD17 -集落形成细胞。这是首次明确证明肥大细胞直接由早期造血祖细胞补充，因此在造血系统中形成了一个独特的细胞谱系。
