Kitazawa S, Ross F P, McHugh K, Teitelbaum S L
Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110.
J Biol Chem. 1995 Feb 24;270(8):4115-20. doi: 10.1074/jbc.270.8.4115.
Osteoclastic bone resorption is dependent upon cell-matrix recognition. This process is mediated by the integrin alpha v beta 3 whose expression is enhanced, in avian osteoclast precursors, by bone-seeking steroids. The purpose of this study was to determine if bone-modulating cytokines impact on alpha v beta 3 expression by mouse marrow macrophages (BMMs), known to differentiate into osteoclasts. Of the cytokines tested. Interleukin-4 (IL-4) is most effective in increasing beta 3 mRNA levels by a mechanism involving transactivation of the beta 3 gene. Moreover, IL-4 augmented beta 3 mRNA is mirrored by plasma membrane appearance of alpha v beta 3. As IL-4 induces beta 3 and not alpha v mRNA, the beta 3 chain appears to regulate surface expression of the heterodimer. The functional significance of IL-4-induced alpha v beta 3 is underscored by the fact that, while attachment to fibronectin is unaltered, treatment of BMMs with the cytokine enhances alpha v beta 3-mediated binding to vitronectin 5-fold. Expression of this heterodimer by BMMs driven along a non-osteoclastic lineage suggests alpha v beta 3 may play a role in the inflammatory response of macrophages.
破骨细胞性骨吸收依赖于细胞与基质的识别。这一过程由整合素αvβ3介导，在禽类破骨细胞前体中，趋骨性类固醇可增强其表达。本研究的目的是确定骨调节细胞因子是否会影响已知可分化为破骨细胞的小鼠骨髓巨噬细胞（BMMs）的αvβ3表达。在所测试的细胞因子中，白细胞介素-4（IL-4）通过涉及β3基因反式激活的机制，在增加β3 mRNA水平方面最为有效。此外，IL-4增加的β3 mRNA与αvβ3在质膜上的出现相对应。由于IL-4诱导的是β3而不是αv mRNA，β3链似乎调节异二聚体的表面表达。IL-4诱导的αvβ3的功能意义在于，虽然与纤连蛋白的附着未改变，但用该细胞因子处理BMMs可使αvβ3介导的与玻连蛋白的结合增强5倍。沿非破骨细胞谱系驱动的BMMs对这种异二聚体的表达表明αvβ3可能在巨噬细胞的炎症反应中起作用。
