Füreder W, Agis H, Willheim M, Bankl H C, Maier U, Kishi K, Müller M R, Czerwenka K, Radaszkiewicz T, Butterfield J H, Klappacher G W, Sperr W R, Oppermann M, Lechner K, Valent P
Department of Internal Medicine, University of Vienna, Austria.
J Immunol. 1995 Sep 15;155(6):3152-60.
Complement-dependent activation of immune cells is regulated by cell surface membrane receptors. In this study, expression of complement receptors (CR) on human blood basophils (n = 11), tissue mast cells (lung, n = 7; skin, n = 10; uterus, n = 4; tonsil, n = 3; heart, n = 10), and on respective human cell lines (basophil line KU-812, mast cell line HMC-1) was analyzed by the use of mAbs and indirect immunofluorescence. Normal blood basophils and KU-812 cells were found to express C5aR (CD88), membrane cofactor protein (CD46), decay-accelerating factor (CD55), and membrane attack complex inhibitory factor (CD59), as well as the previously recognized CR1 (CD35), CR3 alpha (CD11b), CR4 alpha (CD11c), and CR3/4 beta (CD18). Mast cells from all organs as well as HMC-1 cells expressed CD46, CD55, and CD59, but not CD11b, CD21, or CD35. The C5aR (CD88) was detectable on skin mast cells, a subset (5 to 15%) of cardiac mast cells, and on HMC-1 cells, but not on lung, uterus, or tonsillar mast cells (< 5%). Moreover, double immunoperoxidase staining (tryptase vs C5aR/CD88) revealed in situ expression of C5aR on skin, but not lung mast cells. Recombinant human (rh) C5a, at 10(-10) to 10(-7) M, induced secretion of histamine from basophils (rhC5a, 10(-8) M: 53.4 +/- 3.1% vs control < 5%) and from skin mast cells (rhC5a, 10(-8) M: 25.8 +/- 16.1% vs control < 10% histamine release), but not from other mast cells (rhC5a or control: < 10%, p > 0.05). The rhC5a-induced secretion of histamine from basophils and skin mast cells was inhibited by S5/1, a blocking Ab against CD88 (basophils: 37.2% to 75.1%; skin mast cells: 39.2% to 83.9% inhibition, p < 0.05). Together, this study shows that a) basophils and mast cells express a different profile of complement receptors, b) C5a-dependent mediator release in skin mast cells and basophils is mediated via CD88, and c) mast cells constitute a heterogeneous lineage in terms of expression of the C5a binding site CD88.
免疫细胞的补体依赖性激活受细胞表面膜受体调控。在本研究中，通过单克隆抗体和间接免疫荧光分析了补体受体（CR）在人血嗜碱性粒细胞（n = 11）、组织肥大细胞（肺，n = 7；皮肤，n = 10；子宫，n = 4；扁桃体，n = 3；心脏，n = 10）以及相应的人细胞系（嗜碱性粒细胞系KU - 812、肥大细胞系HMC - 1）上的表达。发现正常血嗜碱性粒细胞和KU - 812细胞表达C5aR（CD88）、膜辅助因子蛋白（CD46）、衰变加速因子（CD55）和膜攻击复合物抑制因子（CD59），以及先前已识别的CR1（CD35）、CR3α（CD11b）、CR4α（CD11c）和CR3/4β（CD18）。来自所有器官的肥大细胞以及HMC - 1细胞表达CD46、CD55和CD59，但不表达CD11b、CD21或CD35。C5aR（CD88）在皮肤肥大细胞、一部分（5%至15%）心脏肥大细胞以及HMC - 1细胞上可检测到，但在肺、子宫或扁桃体肥大细胞上未检测到（<5%）。此外，双重免疫过氧化物酶染色（类胰蛋白酶与C5aR/CD88）显示C5aR在皮肤而非肺肥大细胞上原位表达。重组人（rh）C5a，浓度为10⁻¹⁰至10⁻⁷M时，可诱导嗜碱性粒细胞（rhC5a，10⁻⁸M：53.4±3.1%，而对照组<5%）和皮肤肥大细胞（rhC5a，10⁻⁸M：25.8±16.1%，而对照组组胺释放<10%）释放组胺，但不能诱导其他肥大细胞释放组胺（rhC5a或对照组：<10%，p>0.05）。抗CD88的阻断抗体S5/1可抑制rhC5a诱导的嗜碱性粒细胞和皮肤肥大细胞组胺释放（嗜碱性粒细胞：37.2%至75.1%；皮肤肥大细胞：39.2%至83.9%抑制，p<0.05）。总之，本研究表明：a）嗜碱性粒细胞和肥大细胞表达不同的补体受体谱；b）皮肤肥大细胞和嗜碱性粒细胞中C5a依赖性介质释放是通过CD88介导的；c）就C5a结合位点CD88的表达而言，肥大细胞构成一个异质性谱系。
