Levi-Schaffer F, Mekori Y A, Segal V, Claman H N
Department of Pharmacology, Hebrew University, Hadassah Medical School, Jerusalem, Israel.
Cell Immunol. 1990 Apr 15;127(1):146-58. doi: 10.1016/0008-8749(90)90121-7.
There is growing interest in studying pathways of mast cell activation. In a mouse model of chronic graft-vs-host disease (cGVHD) extensive mast cell activation and degranulation occurs in vivo coincident with the development of dermal fibrosis. An interesting feature of this model is that the mast cell reaction is slow to develop, occurring over a period of weeks and waning by 300 days. The aim of our work was to investigate the effects of supernatants from splenocytes of such cGVHD mice (cGVHD sups) on mouse and rat peritoneal mast cells cocultured with 3T3 skin fibroblasts. We found that cGVHD sups are able to release histamine from both mouse and rat cultured mast cells in a slow fashion. Histamine release became evident only after 5-8 days of coculture of the mast cells with the cGVHD supernatants and thereafter decreased to basal levels. Mast cell activation due to cGVHD supernatants was a noncytotoxic event as demonstrated by mast cell counts in the cocultures and by the ability of mast cells to exclude trypan blue. Mast cells that had been activated by incubation with the cGVHD sups were as responsive to stimulation with either anti-IgE antibodies or compound 48/80 as were mast cells incubated with control sups. Supernatants from mice early in GVHD (Days 11-28) were most active in promoting histamine release. Supernatants from spleens of mice which had GVHD for 290 days and where the mast cells had returned to full granulation in vivo were inactive. This is the first in vitro study demonstrating slow mast cell histamine release instituted by other cells, namely the splenocytes of cGVHD mice.
对肥大细胞激活途径的研究兴趣与日俱增。在慢性移植物抗宿主病（cGVHD）的小鼠模型中，体内会发生广泛的肥大细胞激活和脱颗粒，这与皮肤纤维化的发展同时出现。该模型的一个有趣特征是肥大细胞反应发展缓慢，持续数周，到300天时逐渐减弱。我们研究的目的是探讨此类cGVHD小鼠脾细胞的上清液（cGVHD sups）对与3T3皮肤成纤维细胞共培养的小鼠和大鼠腹膜肥大细胞的影响。我们发现，cGVHD sups能够缓慢地从小鼠和大鼠培养的肥大细胞中释放组胺。只有在肥大细胞与cGVHD上清液共培养5 - 8天后，组胺释放才变得明显，此后降至基础水平。如共培养中的肥大细胞计数以及肥大细胞排除台盼蓝的能力所示，cGVHD上清液引起的肥大细胞激活是非细胞毒性事件。用cGVHD sups孵育激活的肥大细胞，与用对照上清液孵育的肥大细胞一样，对抗IgE抗体或化合物48/80的刺激有反应。GVHD早期（第11 - 28天）小鼠的上清液在促进组胺释放方面最活跃。患有GVHD 290天且体内肥大细胞已恢复完全颗粒化的小鼠脾脏的上清液没有活性。这是第一项体外研究，证明了由其他细胞（即cGVHD小鼠的脾细胞）引发的肥大细胞组胺缓慢释放。
