Cellular expression of the C5a anaphylatoxin receptor (C5aR): demonstration of C5aR on nonmyeloid cells of the liver and lung.
Cellular expression of the C5a anaphylatoxin receptor (C5aR): demonstration of C5aR on nonmyeloid cells of the liver and lung.
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DOI：
10.4049/jimmunol.154.4.1861
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发表时间：
1995-02
影响因子：
4.4
通讯作者：
D. Haviland;R. McCoy;W. Whitehead;Hideto Akama;E. Molmenti;A. Brown;J. Haviland;W. Parks;D. Perlmutter;R. Wetsel
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文献类型：
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作者：
D. Haviland;R. McCoy;W. Whitehead;Hideto Akama;E. Molmenti;A. Brown;J. Haviland;W. Parks;D. Perlmutter;R. Wetsel
小补体C5激活片段C5a是一种有效的炎性分子，其在与C5a受体（C5aR）结合时介导平滑肌收缩，增强血管通透性，并促进白细胞功能，如定向趋化性、脱粒、介质释放和超氧阴离子的产生。虽然C5aR的表达传统上被认为是主要局限于骨髓血细胞，包括中性粒细胞，单核细胞，巨噬细胞，嗜酸性粒细胞，我们在这里报告，C5aR表达的肝细胞和肺细胞，以及在其他几个组织中的细胞。通过北方印迹分析，确定小鼠肝脏、狒狒肝脏、人肝脏和人肝癌衍生细胞系HepG2表达正常大小（2.3 kb）的C5aR mRNA;在HepG2细胞中，C5aR mRNA的量与dbcAMP分化的U937细胞中所含的量相当。通过流式细胞术和免疫荧光分析以及125I-C5a结合试验证明HepG2细胞在其细胞表面上表达C5aR。结合数据表明，HepG2细胞表达单一类别的C5aR，Kd为1.18 nM，每个细胞约有28，000个受体。通过原位杂交和免疫组织化学分析证实了C5aR在人肝细胞中的体内表达。小鼠和狒狒器官的北方印迹分析表明，除了肝脏，其他组织表达C5aR mRNA的显着量，包括脾，肺，心脏，肾，和肠。此外，用LPS处理的小鼠在除肠外的所有这些组织中显示C5aR mRNA的大幅增加。人肺组织的免疫染色表明，支气管和肺泡上皮细胞，以及血管平滑肌和内皮细胞，也表达C5aR。总的来说，这些数据表明C5aR在肝和肺中的几种不同类型的细胞中表达，并且在脾、心脏、肠和肾中的尚未确定的细胞类型中表达。此外，这些数据表明，C5a过敏毒素介导以前未认识到的功能，结合组织细胞表达C5aR。
The small-complement C5 activation fragment, C5a, is a potent phlogistic molecule that, on binding to the C5a Receptor (C5aR), mediates contraction of smooth muscle, enhances vascular permeability, and promotes leukocyte functions such as directed chemotaxis, degranulation, mediator release, and production of superoxide anions. Although C5aR expression has traditionally been thought to be limited primarily to myeloid blood cells, including neutrophils, monocytes, macrophages, and eosinophils, we report here that C5aR is expressed by liver and lung cells as well as by cells in several other tissues. By Northern blot analysis, it was determined that mouse liver, baboon liver, human liver, and the human hepatoma-derived cell line HepG2 express a normal size (2.3 kb) C5aR mRNA; in HepG2 cells, the quantity of C5aR mRNA was comparable to that contained in dbcAMP-differentiated U937 cells. HepG2 cells were demonstrated to express the C5aR on their cell surface by flow cytometric and immunofluorescence analyses as well as by 125I-C5a binding assays. The binding data indicated that HepG2 cells express a single class of C5aR with a Kd of 1.18 nM and approximately 28,000 receptors per cell. In vivo expression of C5aR in human liver cells was demonstrated by in situ hybridization and immunohistochemistry analyses. Northern blot analysis of murine and baboon organs shows that, in addition to the liver, other tissues express C5aR mRNA in significant quantities, including the spleen, lung, heart, kidney, and intestine. Moreover, mice treated with LPS show a large increase in C5aR mRNA in all these tissues except the intestine. Immunostaining of human lung tissue demonstrated that bronchial and alveolar epithelial cells, as well as vascular smooth muscle and endothelial cells, also express the C5aR. Collectively, these data indicate that the C5aR is expressed in several different types of cells in liver and lung, and in yet undetermined cell types in spleen, heart, intestine, and kidney. Furthermore, these data suggest that the C5a anaphylatoxin mediates previously unrecognized functions by binding to tissue cells that express the C5aR.