Weiler J M, Edens R E, Bell C S, Gleich G J
Iowa City VA Medical Center, Iowa, USA.
Immunology. 1995 Feb;84(2):213-9.
Major basic protein, the primary constituent of eosinophil granules, regulates the alternative and classical pathways of complement. Major basic protein and other eosinophil granule cationic proteins, which are important in mediating tissue damage in allergic disease, regulate the alternative pathway by interfering with C3b interaction with factor B to assemble an alternative pathway C3 convertase. In the present study, eosinophil peroxidase, eosinophil cationic protein and eosinophil-derived neurotoxin, as well as major basic protein, were examined for capacity to regulate the classical pathway. Eosinophil peroxidase, eosinophil cationic protein and major basic protein inhibited formation of cell-bound classical pathway C3 convertase (EAC1,4b,2a), causing 50% inhibition of complement-mediated lysis at about 0.19, 0.75 and 0.5 micrograms/10(7) cellular intermediates, respectively. Eosinophil-derived neurotoxin had no activity on this pathway of complement. The eosinophil granule proteins were examined for activity on the formation of the membrane attack complex. Major basic protein and eosinophil cationic protein had no activity on terminal lysis. In contrast, eosinophil peroxidase inhibited lysis of EAC1,4b,2a,3b,5b, but had only minimal activity on later events in complement lysis. These polycations were then examined to determine the site(s) at which they regulated the early classical pathway. Eosinophil granule polycationic proteins: (1) reduced the Zmax at all time points but had only minimal effect on the Tmax during the formation of the classical pathway C3 convertase (EAC1,4b,2a); (2) inhibited formation of EAC1,4b,2a proportional to C4 but independent of C2 concentration; (3) inhibited fluid phase formation of C1,4b,2a, as reflected by a decrease in C1-induced consumption of C2 over time; and (4) inhibited C1 activity over time without a direct effect on either C4 or C2. These observations suggest that polycations regulate the early classical pathway by interfering with C1 and may exert this activity in vivo.
主要碱性蛋白是嗜酸性粒细胞颗粒的主要成分，可调节补体的替代途径和经典途径。主要碱性蛋白及其他嗜酸性粒细胞颗粒阳离子蛋白在介导过敏性疾病中的组织损伤方面具有重要作用，它们通过干扰C3b与B因子的相互作用来组装替代途径C3转化酶，从而调节替代途径。在本研究中，对嗜酸性粒细胞过氧化物酶、嗜酸性粒细胞阳离子蛋白、嗜酸性粒细胞衍生神经毒素以及主要碱性蛋白调节经典途径的能力进行了检测。嗜酸性粒细胞过氧化物酶、嗜酸性粒细胞阳离子蛋白和主要碱性蛋白抑制细胞结合的经典途径C3转化酶（EAC1,4b,2a）的形成，分别在约0.19、0.75和0.5微克/10⁷个细胞中间体时导致补体介导的溶解受到50%的抑制。嗜酸性粒细胞衍生神经毒素对补体的这条途径没有活性。检测了嗜酸性粒细胞颗粒蛋白对膜攻击复合物形成的活性。主要碱性蛋白和嗜酸性粒细胞阳离子蛋白对终末溶解没有活性。相比之下，嗜酸性粒细胞过氧化物酶抑制EAC1,4b,2a,3b,5b的溶解，但对补体溶解后期事件的活性极小。然后检测这些多阳离子以确定它们调节早期经典途径的位点。嗜酸性粒细胞颗粒多阳离子蛋白：（1）在所有时间点均降低Zmax，但在经典途径C3转化酶（EAC1,4b,2a）形成过程中对Tmax的影响极小；（2）抑制EAC1,4b,2a的形成与C4成比例，但与C2浓度无关；（3）抑制C1,4b,2a的液相形成，表现为随着时间推移C1诱导的C2消耗减少；（4）随着时间推移抑制C1活性，而对C4或C2均无直接影响。这些观察结果表明，多阳离子通过干扰C1来调节早期经典途径，并且可能在体内发挥这种活性。
