Kaufmann J, Jorgensen R W, Martin B M, Franzblau C
Department of Biochemistry, Boston University School of Medicine, MA 02118.
Atherosclerosis. 1990 Dec;85(2-3):113-25. doi: 10.1016/0021-9150(90)90103-p.
Mononuclear phagocytes adhere to and penetrate the vessel wall endothelium and contact the subendothelial space prior to the development of the atherosclerotic plaque. In an attempt to model the early events of plaque development we used an elastin-rich, multicomponent, cell-derived matrix from neonatal rat aortic smooth muscle cells as a substratum for monocytes. Using this model, we show that human monocyte morphology and metabolism are markedly altered by the matrix substratum. When a mixed mononuclear cell population is seeded on matrix or plastic, only monocytes adhere to the matrix surface. In contrast, lymphocytes as well as monocytes adhere to the plastic surface. The matrix-adherent monocytes develop large intracellular granules and form extensive clusters of individual cells. Metabolically, these cells develop sodium fluoride resistant non-specific esterase activity and their media contain more growth factor activity and PGE2. Although total protein synthesis is equivalent in both cultures, the matrix contact induces an increase in specific proteins in the media. We also show that a purified alpha-elastin substratum induces some, but not all, of the monocyte changes seen when using the matrix substratum. Using the alpha-elastin substratum, there is selective adhesion of monocytes and increased growth factor activity, however, the cells are morphologically different from the matrix-adherent cells. Thus, the use of the smooth muscle cell-derived matrix, in conjunction with purified matrix components, serves as a model that can provide insight into the mechanisms of monocyte adhesion and stimulation by the matrix environment that exists in vivo. Such mechanisms may be particularly important in atherogenesis.
在动脉粥样硬化斑块形成之前，单核吞噬细胞会黏附并穿透血管壁内皮，接触内皮下间隙。为了模拟斑块形成的早期事件，我们使用了来自新生大鼠主动脉平滑肌细胞的富含弹性蛋白的多组分细胞衍生基质作为单核细胞的底物。利用这个模型，我们发现基质底物会显著改变人类单核细胞的形态和代谢。当将混合单核细胞群体接种在基质或塑料上时，只有单核细胞会黏附在基质表面。相比之下，淋巴细胞和单核细胞都会黏附在塑料表面。黏附在基质上的单核细胞会形成大的细胞内颗粒，并形成大量单个细胞的聚集。在代谢方面，这些细胞会产生耐氟化钠的非特异性酯酶活性，并且它们的培养基含有更多的生长因子活性和前列腺素E2。尽管两种培养物中的总蛋白质合成相当，但与基质的接触会导致培养基中特定蛋白质的增加。我们还表明，纯化的α-弹性蛋白底物会诱导出使用基质底物时所见的部分而非全部单核细胞变化。使用α-弹性蛋白底物时，单核细胞会选择性黏附，生长因子活性增加，然而，这些细胞在形态上与黏附在基质上的细胞不同。因此，将平滑肌细胞衍生基质与纯化的基质成分结合使用，可作为一种模型，有助于深入了解体内存在的基质环境对单核细胞黏附和刺激的机制。这些机制在动脉粥样硬化发生过程中可能尤为重要。
