Macrophage-lymphocyte synergy in the production of osteoclast activating factor.
Macrophage-lymphocyte synergy in the production of osteoclast activating factor.
复制标题
巨噬细胞-淋巴细胞协同产生破骨细胞激活因子。
作者：
J. Horton;J. Oppenheim;S. E. Mergenhagen;L. Raisz
活化的正常人外周血白细胞培养物的上清液含有一种在体外刺激骨细胞骨吸收的因子。本研究表明，破骨细胞活化因子（OAF）产生的植物血凝素激活的单核细胞在6小时内的激活，和峰值生产与增加的氨基酸掺入到蛋白质，但之前增加胸苷掺入到DNA。粒细胞、血小板和红细胞对于OAF的产生不是必需的，因为在Ficoll-Hypaque梯度上纯化的单核细胞并且缺乏这些元素产生的OAF与未分离的白细胞一样多。粒细胞提取物未显示骨吸收活性。单个核细胞的OAF产生受到辐射的损害，这表明它是由辐射敏感的淋巴细胞，而不是辐射抗性的巨噬细胞。然而，OAF不产生的玻璃珠柱上纯化的淋巴细胞，虽然这些细胞可以响应增加胸苷和氨基酸掺入植物血凝素。纯化的巨噬细胞也未能产生实质性的骨吸收活性。然而，当将少量经辐照但存活的巨噬细胞（5 × 104个细胞/ml）加入到玻璃珠纯化的淋巴细胞（2 × 106个细胞/ml）中时，OAF的产生与未分离的单核细胞群体一样大。这些结果表明，OAF是由淋巴细胞，但它的生产是依赖于巨噬细胞-淋巴细胞的相互作用。OAF是一种独特的骨吸收因子，可能在慢性炎症和肿瘤相关的骨病变中发挥重要作用。其产生的细胞机制参与这些疾病的发病机制。
Supernatants from cultures of activated normal human peripheral blood leukocytes contain a factor which stimulates osteoclastic bone resorption in vitro. The present study indicates that osteoclast activating factor (OAF) is produced by phytohemagglutinin-activated mononuclear cells within 6 hr of activation, and that peak production is associated with increased amino acid incorporation into protein but precedes increased thymidine incorporation into DNA. Granulocytes, platelets, and red cells were not necessary for the production of OAF, since mononuclear cells purified on Ficoll-Hypaque gradients and devoid of these elements produced as much OAF as unseparated leukocytes. Granulocyte extracts did not show bone-resorbing activity. The production of OAF by mononuclear cells was impaired by irradiation, suggesting that it is made by radiosensitive lymphocytes rather than radioresistant macrophages. However, OAF was not produced by lymphocytes purified on glass-bead columns although these cells could respond to phytohemagglutinin with increased thymidine and amino acid incorporation. Purified macrophages also failed to produce substantial bone-resorbing activity. However, when a small number of irradiated but viable macrophages (5 × 104 cells/ml) was added to glass bead-purified lymphocytes (2 × 106 cells/ml), OAF production was as great as with unseparated mononuclear cell populations. These results suggest that OAF is produced by lymphocytes, but that its production is dependent on macrophage-lymphocyte interaction. OAF is a unique bone-resorbing factor which may play an important role in bone lesions associated with chronic inflammation and neoplasia. The cellular mechanisms for its production participate in the pathogenesis of these disorders.