Butterworth A E, Vadas M A, Wassom D L, Dessein A, Hogan M, Sherry B, Gleich G J, David J R
J Exp Med. 1979 Dec 1;150(6):1456-71. doi: 10.1084/jem.150.6.1456.
Previous work (1)(1) has shown that normal human eosinophils show a preferential capacity, in comparison with neutrophils, to bind to antibody- coated schistosomula of Schistosoma mansoni. This effect is attributable to a temperature-dependent function of the eosinophil which renders its binding stable and irreversible by aggregated gamma globulin or Staphylococcus aureus protein A. In contrast, the binding of neutrophils is readily reversible by these agents. It has now been shown that the differences observed between eosinophils and neutrophils is a property of their interaction with living schistosomula. When dead or artificially damaged schistosomula were tested, neutrophils showed a markedly enhanced capacity to adhere, in both the presence and absence of anti-chistosomular serum. Subsequent experiments were designed to test the hypothesis that the strong, stable binding of eosinophils was attributable to degranulation, with release of granule contents which would then serve as ligands to bind the cell to the organism. First, an enhanced adherence both of eosinophils and of neutrophils could be demonstrated in the presence of eosinophil major basic protein (MBP) or of protamine, a high molecular weight cation. Second, the binding of eosinophils induced by concanavalin A (Con A) was found to differ markedly from that induced by antischistosomular serum. Con A-mediated binding of eosinophils was fully reversible by alpha-methyl-mannoside, was not associated with damage to the organism, and did not lead to degranulation of the cell, as estimated by measuring the release of MBP into the culture supernate. However, induction of degranulation of concanavalin A-bound eosinophils, but not of neutrophils, with the calcium ionophore A23187 converted the reaction into one which was no longer reversible by alpha- methylmannoside and in which damage to the organism now did occur. These findings support the hypothesis that the stable binding of eosinophils is associated with degranulation, a process which may contribute to the preferential capacity of this cell to mediate antibody-dependent damage to schistosomula.
以往的研究(参考文献1)表明,与中性粒细胞相比,正常人嗜酸性粒细胞具有优先结合曼氏血吸虫抗体包被的童虫的能力。这种效应归因于嗜酸性粒细胞的一种温度依赖性功能,该功能使其与聚集的γ球蛋白或金黄色葡萄球菌蛋白A的结合稳定且不可逆。相比之下,中性粒细胞的结合可被这些试剂轻易逆转。现已表明,嗜酸性粒细胞和中性粒细胞之间观察到的差异是它们与活童虫相互作用的一种特性。当测试死的或人工损伤的童虫时,无论有无抗血吸虫血清,中性粒细胞的黏附能力都显著增强。随后设计了实验来检验以下假设:嗜酸性粒细胞的强而稳定的结合归因于脱颗粒,颗粒内容物的释放随后作为配体将细胞与生物体结合。首先,在嗜酸性粒细胞主要碱性蛋白(MBP)或鱼精蛋白(一种高分子量阳离子)存在的情况下,可以证明嗜酸性粒细胞和中性粒细胞的黏附均增强。其次,发现伴刀豆球蛋白A(Con A)诱导的嗜酸性粒细胞结合与抗血吸虫血清诱导的结合明显不同。Con A介导的嗜酸性粒细胞结合可被α-甲基甘露糖苷完全逆转,与生物体损伤无关,且不会导致细胞脱颗粒,这是通过测量MBP释放到培养上清液中来估计的。然而,用钙离子载体A23187诱导Con A结合的嗜酸性粒细胞而非中性粒细胞脱颗粒,会使反应转变为不再能被α-甲基甘露糖苷逆转的反应,并且此时确实会发生对生物体的损伤。这些发现支持了以下假设:嗜酸性粒细胞的稳定结合与脱颗粒有关,这一过程可能有助于该细胞介导抗体依赖性对童虫损伤的优先能力。