Hamada A, Greene B M
J Immunol. 1987 Feb 15;138(4):1240-5.
Antibody-dependent eosinophil-mediated cytotoxicity plays a role in host protection against metazoan parasite invasion. We examined a possible role for Clq in eosinophil-mediated cytotoxicity by using a Schistosoma mansoni schistosomula killing system in vitro. The addition of monomeric purified human Clq enhanced IgG-dependent human eosinophil-mediated killing from 1.4-fold to 2.3-fold (mean percent killing 12% +/- 4 vs 21% +/- 4, p less than 0.005) when the immune IgG concentration was low. In contrast, there was no significant enhancement of neutrophil-mediated killing. When the IgG concentration was increased fourfold Clq did not cause enhancement of eosinophil-mediated killing (35% +/- 9 vs 37% +/- 5). Preincubation of eosinophils with type 1 collagen abrogated Clq enhancement of killing, raising the possibility of a receptor-mediated process, which depends upon cellular binding of Clq via the collagenous portion of the molecule. Eosinophils and neutrophils were examined for the presence of Clq receptors by using 125I labeled Clq. Clq binding to both cell types was saturable, reversible, and specific, indicating that binding is through specific receptors. Type 1 collagen inhibited binding of Clq to cells, suggesting that Clq binding is via the collagenous stalk of Clq. The number of receptors was approximately twice as high for eosinophils as compared with neutrophils (1.9 X 10(7) vs 1.1 X 10(7), p less than 0.025). Affinity constants for the two cell types were similar (1.5 X 10(7) vs 1.3 X 10(7). These findings suggest that Clq and receptors for Clq on eosinophils may be important for eosinophil-mediated schistosomula killing.
抗体依赖的嗜酸性粒细胞介导的细胞毒性在宿主抵御后生动物寄生虫入侵的保护过程中发挥作用。我们通过使用体外曼氏血吸虫童虫杀伤系统,研究了补体C1q在嗜酸性粒细胞介导的细胞毒性中可能发挥的作用。当免疫IgG浓度较低时,添加单体纯化的人补体C1q可使IgG依赖的人嗜酸性粒细胞介导的杀伤作用增强1.4倍至2.3倍(平均杀伤百分比为12%±4对21%±4,p<0.005)。相比之下,对中性粒细胞介导的杀伤作用没有显著增强。当IgG浓度增加四倍时,补体C1q并未导致嗜酸性粒细胞介导的杀伤作用增强(35%±9对37%±5)。嗜酸性粒细胞与I型胶原预孵育可消除补体C1q对杀伤作用的增强,这增加了一种受体介导过程的可能性,该过程依赖于补体C1q通过分子的胶原部分与细胞结合。通过使用125I标记的补体C1q检测嗜酸性粒细胞和中性粒细胞中补体C1q受体的存在情况。补体C1q与两种细胞类型的结合是可饱和的、可逆的和特异性的,表明这种结合是通过特异性受体进行的。I型胶原抑制补体C1q与细胞的结合,提示补体C1q的结合是通过补体C1q的胶原柄进行的。嗜酸性粒细胞的受体数量大约是中性粒细胞的两倍(1.9×107对1.1×107,p<0.025)。两种细胞类型的亲和常数相似(1.5×107对1.3×107)。这些发现表明,补体C1q及其在嗜酸性粒细胞上的受体可能对嗜酸性粒细胞介导的童虫杀伤作用很重要。