Aminoalkylbisphosphonates, potent inhibitors of bone resorption, induce a prolonged stimulation of histamine synthesis and increase macrophages, granulocytes, and osteoclasts in vivo
Aminoalkylbisphosphonates, potent inhibitors of bone resorption, induce a prolonged stimulation of histamine synthesis and increase macrophages, granulocytes, and osteoclasts in vivo
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氨基烷基双膦酸盐是骨吸收的有效抑制剂，可诱导组胺合成的长期刺激并增加体内巨噬细胞、粒细胞和破骨细胞的数量
DOI：
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发表时间：
1993
影响因子：
4.2
通讯作者：
K. Kumagai
中科院分区：
文献类型：
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作者：
Y. Endo;Masanori Nakamura;T. Kikuchi;H. Shinoda;Y. Takeda;Y. Nitta;K. Kumagai
摘要二膦酸盐的氨基烷基衍生物是骨吸收的有效抑制剂。单一IP注射 4-氨基-1-羟基丁亚基-1,1-二膦酸酯 (AHBuBP) 会诱导小鼠骨髓、脾脏、肺和肝脏中组氨酸脱羧酶 (HDC) 活性持续增强，并导致组胺增加。该药物对 HDC 的诱导具有剂量依赖性（16-80 μmol/kg），并在注射后 3-4 天达到峰值（40 μmol/kg）。皮下重复注射较小剂量的 AHBuBP（0.32 或 1.6 μmol/kg/天）4 天也增强了 HDC 活性。然而，抑制骨吸收的最小剂量（0.064 μmol/kg/天）低于诱导HDC的剂量。出乎意料的是，AHBuBP 在诱导 HDC 的剂量下，增加了巨噬细胞、粒细胞甚至破骨细胞的数量。破骨细胞的尺寸也因该试剂而增大。另一种氨基二膦酸盐，3-氨基-1-羟基亚丙基-1,1-二膦酸盐，但没有九氨基衍生物，也表现出与AHBuBP基本相同的效果。这些结果表明，尽管破骨细胞增加且增大，但氨基二膦酸盐仍然抑制骨吸收。由于粒细胞和粒细胞-巨噬细胞集落刺激因子和白细胞介素-3在造血器官中诱导HDC，而组胺具有造血活性，因此氨基二磷酸盐诱导HDC可能与巨噬细胞、粒细胞和破骨细胞祖细胞的增殖有关。
SummaryAminoalkyl derivatives of bisphosphonates are potent inhibitors of bone resorption. A single I.P. injection of 4-amino-1-hydroxybutylidene-1,1-bis-phosphonate (AHBuBP) induced a prolonged enhancement of histidine decarboxylase (HDC) activity in the bone marrow, spleen, lung, and liver of mice and resulted in an increase in histamine. The induction of HDC by the agent was dose dependent (16–80 μmol/kg) and peaked 3–4 days after its injection (40 μmol/kg). Repeated S.C. injections of smaller doses of AHBuBP (0.32 or 1.6 μmol/kg/day) for 4 days also enhanced HDC activity. However, the minimum dose capable of inhibiting bone resorption (0.064 μmol/kg/day) was lower than that inducing HDC. Unexpectedly, AHBuBP, at the doses inducing HDC, increased macrophages, granulocytes, and even osteoclasts. The size of osteoclasts was also enlarged by the agent. Another aminobisphosphonate, 3-amino-1-hydroxypropylidene-1,1-bisphosphonate, but none of nonamino derivatives, also exhibited essentially the same effects as those of AHBuBP. These results indicate that in spite of increase in osteoclasts and their enlargement, bone resorption is still inhibited by amino bisphosphonates. As granulocyte and granulocyte-macrophage colony-stimulating factors and interleukin-3 induce HDC in hematopoietic organs, and histamine has a hematopoietic activity, the HDC induction by aminobisphosphonates may be relevant to the proliferation of progenitor cells of macrophages, granulocytes, and osteoclasts.
影响因子：
15.9
作者：
CARANO, A;TEITELBAUM, SL;BLAIR, HC
通讯作者：
BLAIR, HC
影响因子：
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作者：
DINARELLO, CA
通讯作者：
DINARELLO, CA