Lipid bodies: cytoplasmic organelles important to arachidonate metabolism in macrophages and mast cells.

Lipid bodies: cytoplasmic organelles important to arachidonate metabolism in macrophages and mast cells.
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DOI:
10.4049/jimmunol.131.6.2965
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发表时间:
1983-12
影响因子:
4.4
通讯作者:
AM Dvorak;HF Dvorak;SP Peters;ES Shulman;DW MacGlashan;K. Pyne;VS Harvey;SJ Galli;LM Lichtenstein
AM Dvorak;HF Dvorak;SP Peters;ES Shulman;DW MacGlashan;K. Pyne;VS Harvey;SJ Galli;LM Lichtenstein
中科院分区:
医学2区
文献类型:
--
作者:
AM Dvorak;HF Dvorak;SP Peters;ES Shulman;DW MacGlashan;K. Pyne;VS Harvey;SJ Galli;LM Lichtenstein

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关于花生四烯酸(AA)氧化产物的生物化学性质和药理学活性已经了解了很多,但对AA被纳入其中的有核细胞中的结构以及AA最初被动员的结构知之甚少。为了解决这个问题,我们在体外给予人肺肥大细胞和肺泡巨噬细胞以及小鼠和豚鼠腹腔巨噬细胞3 H-AA或其他3 H-脂肪酸。3 H标记的亚细胞分布进行了评估,通过电子显微镜放射自显影,并通过薄层色谱法测定细胞相关的3 H-脂质的性质。人肺肥大细胞的放射自显影分析定位几乎所有的3 H-AA的细胞质脂质体。脂质体大致呈球形,可变的嗜锇性,非膜结合结构,出现在各种细胞的细胞质中,但我们发现,这些脂质体出现在粒细胞,巨噬细胞和肥大细胞的炎症,免疫或肿瘤过程的网站频率增加。大环内酯还主要将3 H-AA掺入细胞质脂质体中。然而,与肥大细胞相反,巨噬细胞也将3 H-AA掺入质膜中。刺激巨噬细胞吞噬导致脂质体与细胞内膜的关系发生显著变化,因此许多脂质体出现在吞噬溶酶体附近。此外,一些吞噬溶酶体含有3 H标记,这沿着其他形态学证据表明,脂质体可能将其内容物排入这些结构。肥大细胞和巨噬细胞胞质脂质体似乎代表了AA和可能从外部环境中摄取的其他脂肪酸的产物的细胞内储存和代谢的主要位点。因此,这些迄今被忽视的细胞器可能会影响各种适应性或病理过程中的细胞功能。
Much has been learned about the biochemical nature and pharmacologic activity of the products of arachidonic acid (AA) oxidation, but relatively little is known about the structures in nucleated cells into which AA is incorporated and from which it is initially mobilized. To address this question, we administered 3H-AA or other 3H-fatty acids in vitro to human lung mast cells and alveolar macrophages as well as to mouse and guinea pig peritoneal macrophages. The subcellular distribution of 3H label was assessed by electron microscopic autoradiography, and the nature of cell-associated 3H-lipids was determined by thin layer chromatography. Autoradiographic analysis of human lung mast cells localized virtually all of the 3H-AA to cytoplasmic lipid bodies. Lipid bodies are roughly spherical, variable osmiophilic, nonmembrane-bound structures that appear in the cytoplasm of a wide variety of cells, but we have found that these lipid bodies occur with increased frequency in granulocytes, macrophages, and mast cells at sites of inflammatory, immunologic, or neoplastic processes. Macrophages also incorporated 3H-AA predominantly into cytoplasmic lipid bodies. In contrast to mast cells, however, macrophages incorporated 3H-AA into the plasma membrane as well. Stimulation of macrophage phagocytosis resulted in striking alterations of the relationships of lipid bodies to intracellular membranes, so that many lipid bodies appeared adjacent to phagolysosomes. In addition, some phagolysosomes contained 3H label, which along with other morphologic evidence suggested that lipid bodies may discharge their contents into these structures. Mast cell and macrophage cytoplasmic lipid bodies appear to represent a major site of intracellular storage and metabolism of products of AA and perhaps other fatty acids taken up from the external milieu. These heretofore neglected organelles may thus influence cellular function in a wide variety of adaptive or pathologic processes.