Contrast between effects of aminobisphosphonates and non‐aminobisphosphonates on collagen‐induced arthritis in mice
Contrast between effects of aminobisphosphonates and non‐aminobisphosphonates on collagen‐induced arthritis in mice
复制标题
氨基二膦酸盐与非氨基二膦酸盐对小鼠胶原性关节炎的作用对比
DOI：
10.1111/j.1476-5381.1996.tb15972.x
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发表时间：
1996
影响因子：
7.3
通讯作者：
Y. Endo
中科院分区：
文献类型：
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作者：
M. Nakamura;T. Ando;M. Abe;K. Kumagai;Y. Endo
1双膦酸盐（BPs）是骨吸收的抑制剂，许多衍生物已被开发用于治疗骨吸收增强。氨基二膦酸盐（aminobisphosphonates）在这方面特别有效。我们之前已经证明，氨基BP，如4-氨基-1-羟基亚丁基-1，1-二膦酸（AHBuBP），诱导组氨酸脱羧酶，形成组胺的酶，并增加巨噬细胞，粒细胞和破骨细胞的数量。非氨基BP不显示这种活性。2在本研究中，另一种氨基BP，环庚基氨基亚甲基二膦酸酯（CHAMBP），被证明具有与AHBuBP相似的性质，表明这些作用在氨基BP中很常见。3在确定氨基BP是否影响免疫反应的实验中，我们发现CHAMBP和AHBuBP各自加重了通过共注射II型胶原和佐剂诱导的小鼠关节炎，这是类风湿性关节炎的模型。相比之下，二氯亚甲基二膦酸盐（C12 MBP），一种典型的非氨基BP，确实抑制了关节炎。4.根据这些结果和以前获得的结果，我们提出CHAMBP和AHBuBP的加重作用可能与它们刺激组胺合成和增加巨噬细胞和粒细胞的能力有关。相反，我们认为C12 MBP对关节炎的抑制作用与其对巨噬细胞或粒细胞的细胞毒性作用有关。
1 Bisphosphonates (BPs) are inhibitors of bone resorption, and many derivatives have been developed for the treatment of enhanced bone resorption. Aminobisphosphonates (aminoBPs) are particularly potent in this respect. We have shown previously that aminoBPs, such as 4‐amino‐1‐hydroxybutylidene‐1,1‐bisphosphonic acid (AHBuBP), induce histidine decarboxylase, the enzyme forming histamine, and increase macrophages, granulocytes and osteoclast numbers. Non‐aminoBPs do not show this activity. 2 In the present study, an additional aminoBP, cycloheptyl‐aminomethylene bisphosphonate (CHAMBP), was shown to have similar properties to AHBuBP suggesting that these actions are common among aminoBPs. 3 In experiments carried out to determine if aminoBPs affect immune responses, we found that CHAMBP and AHBuBP each exacerbated the arthritis induced in mice by the co‐injection of type II collagen and an adjuvant, a model for rheumatoid arthritis. In contrast, dichloromethylene bisphosphonate (C12MBP), a typical non‐aminoBP, did suppress the arthritis. 4 On the basis of these results, and those obtained previously, we propose that the exacerbating effects of CHAMBP and AHBuBP may be related to their ability to stimulate the synthesis of histamine and to increase macrophages and granulocytes. Conversely, we propose that the suppressive effect of C12MBP on arthritis is related to its cytotoxic action on macrophages or granulocytes.
Yasuo Endo：“通过重组白细胞介素 1 和肿瘤坏死因子诱导小鼠组织中的组氨酸和鸟氨酸脱羧酶活性”Biochem。
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