Ratnoff O D, Gleich G J, Shurin S B, Kazura J, Everson B, Embury P
Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio.
Am J Hematol. 1993 Jan;42(1):138-45. doi: 10.1002/ajh.2830420127.
Several syndromes characterized by striking eosinophilia may be complicated by thrombosis. The experiments described indicate that, paradoxically, eosinophils and certain of their constituents inhibit the activation of Hageman factor (HF, factor XII). In earlier studies, suspensions of mixed types of granulocytes, other nucleated peripheral blood cells, and platelets inhibited activation of Hageman factor by ellagic acid, glass, and sulfatides. After these cells were sedimented by centrifugation, the supernatant fluids were also inhibitory. No attempt had been made earlier to distinguish among different granulocytic species. In the present study, suspensions of eosinophils and the supernatant fluid after eosinophils had been separated by centrifugation inhibited activation of Hageman factor by ellagic acid. The protein concentration of that amount of supernatant fluid that inhibited activation by about half was 16 micrograms/ml, approximately the same as had been described for suspensions of peripheral blood mononuclear cells. Activation of Hageman factor by ellagic acid was also inhibited by certain constituents of eosinophils, including eosinophil peroxidase, eosinophil major basic protein and eosinophil cationic protein. Inhibition was not specific for ellagic acid-induced activation of Hageman factor, as inhibition was also observed with sulfatide-induced activation. Inhibition was presumably related to neutralization of the negative charge of activators of Hageman factor. Thus, bismuth subgallate, a particulate activator of Hageman factor, was no longer effective after it had been exposed to eosinophil cationic protein. The observations reported here raise the question of whether in vivo eosinophils modulate certain of the defense reactions ascribed to Hageman factor.
几种以显著嗜酸性粒细胞增多为特征的综合征可能并发血栓形成。所述实验表明，矛盾的是，嗜酸性粒细胞及其某些成分会抑制哈格曼因子（HF，因子XII）的激活。在早期研究中，混合类型的粒细胞、其他有核外周血细胞和血小板的悬液可抑制鞣花酸、玻璃和硫脂对哈格曼因子的激活。这些细胞经离心沉淀后，上清液也具有抑制作用。早期未尝试区分不同类型的粒细胞。在本研究中，嗜酸性粒细胞悬液以及嗜酸性粒细胞经离心分离后的上清液可抑制鞣花酸对哈格曼因子的激活。抑制激活作用约一半的上清液蛋白浓度为16微克/毫升，与外周血单个核细胞悬液的描述大致相同。嗜酸性粒细胞的某些成分，包括嗜酸性粒细胞过氧化物酶、嗜酸性粒细胞主要碱性蛋白和嗜酸性粒细胞阳离子蛋白，也可抑制鞣花酸对哈格曼因子的激活。这种抑制并非特异性针对鞣花酸诱导的哈格曼因子激活，因为在硫脂诱导的激活中也观察到了抑制作用。抑制作用可能与中和哈格曼因子激活剂的负电荷有关。因此，次没食子酸铋，一种哈格曼因子的颗粒状激活剂，在暴露于嗜酸性粒细胞阳离子蛋白后不再有效。这里报道的观察结果提出了一个问题，即体内嗜酸性粒细胞是否会调节某些归因于哈格曼因子的防御反应。
