Levi-Schaffer F, Segal V, Baram D, Mekori Y A
Department of Pharmacology, School of Pharmacy, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
J Allergy Clin Immunol. 1992 Feb;89(2):501-9. doi: 10.1016/0091-6749(92)90316-t.
We investigated whether murine chronic graft-versus-host disease (cGVHD)-derived skin fibroblasts maintain the viability and functional activity of rat peritoneal connective tissue-mast cells (CTMCs) and whether they affect the change in phenotype of mouse bone marrow-derived mast cells (BMMCs). Skin fibroblasts were isolated before the development of fibrosis (day 5), during overt fibrosis (day 28), and after recovery from fibrosis (day 120). cGVHD fibroblasts of days 5 and 28 exhibited enhanced proliferation, a property that was maintained through several subcultures. CTMCs adhered to the same extent, did not divide, and maintained their viability in all the different cultures. When CTMCs were activated with compound 48/80, they released approximately 80% of their histamine content, indicating that coculture with cGVHD fibroblasts did not adversely affect CTMC function. The amount of histamine found in the medium of 8 days CTMC/cGVHD fibroblast coculture was similar to that found in control culture. These findings suggest that the degranulation of dermal MCs, characteristic of cGVHD, is not due to a direct activating effect of the cGVHD fibroblasts on the MCs. BMMCs seeded on cGVHD fibroblasts acquired the capacity for safranin staining and increased their histamine content, indicative of a change to CTMCs. Thus, cGVHD fibroblasts are able to provide a microenvironment adequate for maintaining viability and activity of CTMCs and for promoting maturation and change in phenotype of BMMCs.
我们研究了源自小鼠慢性移植物抗宿主病(cGVHD)的皮肤成纤维细胞是否能维持大鼠腹膜结缔组织肥大细胞(CTMCs)的活力和功能活性,以及它们是否会影响小鼠骨髓来源肥大细胞(BMMCs)表型的变化。在纤维化发展前(第5天)、明显纤维化期间(第28天)以及从纤维化恢复后(第120天)分离皮肤成纤维细胞。第5天和第28天的cGVHD成纤维细胞表现出增殖增强,这种特性在多次传代培养中得以维持。CTMCs在所有不同培养物中的黏附程度相同,不分裂,并维持其活力。当用化合物48/80激活CTMCs时,它们释放了约其组胺含量的80%,表明与cGVHD成纤维细胞共培养不会对CTMC功能产生不利影响。在CTMCs/cGVHD成纤维细胞共培养8天的培养基中发现的组胺量与对照培养物中的相似。这些发现表明,cGVHD特有的真皮肥大细胞脱颗粒并非由于cGVHD成纤维细胞对肥大细胞的直接激活作用。接种在cGVHD成纤维细胞上的BMMCs获得了番红染色能力并增加了其组胺含量,这表明向CTMCs发生了转变。因此,cGVHD成纤维细胞能够提供一个足以维持CTMCs活力和活性以及促进BMMCs成熟和表型变化的微环境。