Gaither T A, Medley S R, Gallin J I, Frank M M
Inflammation. 1987 Jun;11(2):211-27. doi: 10.1007/BF00916022.
Abnormal phagocyte function in chronic granulomatous disease (CGD) is associated with decreased bactericidal activity. Ingestion of serum-opsonized organisms is reported to be normal in these patients. We previously showed that in CGD the expression of C3b receptors (CR1) on polymorphonuclear leukocytes (PMNs) is significantly depressed. In this study, we compared the phagocytic activity of the PMNs from normal healthy controls with that of CGD patients and one individual with myeloperoxidase (MPO) deficiency. The ingestion of sheep erythrocytes (E) by PMNs adherent to a glass surface was examined; the E were coated either with excess IgG (E-IgG) or with C3b plus limited IgG (EAC3b-IgG). The PMNs, both in CGD and in MPO deficiency, ingested E-IgG and EAC3b-IgG at levels markedly above normal. C3b-coated erythrocytes were not phagocytosed. Preincubating the PMNs with sodium azide, which blocks MPO, or catalase, a scavenger of H2O2, caused a marked increase in phagocytosis by normal PMNs. Azide had a variable effect on PMN activity in CGD and no effect on the activity in the subject with MPO deficiency. Even in the presence of azide, the ingestion of EAC3b-IgG by the PMNs from the CGD patients was significantly greater than that seen in paired normals [mean phagocytic index (PI), 2.13 for CGD vs. 1.48 for normals; P less than 0.05 by the paired sample t test]. Similar results were obtained with ingestion of E-IgG. Notably, ingestion of serum-opsonized Candida organisms (relatively nondegradable particles) was markedly above normal with CGD PMNs and, in normal PMNs, azide treatment also evoked an increase. In addition, rosette formation of the adhered PMNs with E-IgG was enhanced with CGD and the azide-treated normal PMNs. We demonstrated that this increased activity was not the result of increased Fc receptor (FcR) number, as determined from the binding of a monoclonal anti-FcR antibody. Both the E-IgG rosette formation and the ingestion by CGD PMNs were abrogated in the presence of an H2O2-generating system. In contrast, the phagocytic activity of MPO-deficient PMNs was not altered by exogenous H2O2. These findings suggest that cellular products generated by the H2O2-MPO-halide system down-regulate the rosette-forming and phagocytic activity of PMNs from normal healthy individuals, but not that from CGD and MPO-deficient patients.
慢性肉芽肿病（CGD）中吞噬细胞功能异常与杀菌活性降低有关。据报道，这些患者摄入经血清调理的微生物的情况正常。我们之前发现，在CGD中，多形核白细胞（PMN）上C3b受体（CR1）的表达显著降低。在本研究中，我们比较了正常健康对照者、CGD患者以及一名髓过氧化物酶（MPO）缺乏症患者的PMN的吞噬活性。检测了黏附在玻璃表面的PMN对绵羊红细胞（E）的摄取情况；E分别用过量IgG（E-IgG）或C3b加有限量IgG（EAC3b-IgG）包被。CGD患者和MPO缺乏症患者的PMN摄取E-IgG和EAC3b-IgG的水平均明显高于正常水平。C3b包被的红细胞未被吞噬。用叠氮化钠（可阻断MPO）或过氧化氢酶（H2O2的清除剂）预孵育PMN，可使正常PMN的吞噬作用显著增强。叠氮化钠对CGD患者PMN的活性有不同影响，对MPO缺乏症患者的PMN活性无影响。即使在存在叠氮化钠的情况下，CGD患者的PMN摄取EAC3b-IgG的量仍显著高于配对的正常对照者[平均吞噬指数（PI），CGD患者为2.13，正常对照者为1.48；配对样本t检验，P<0.05]。摄取E-IgG时也得到了类似结果。值得注意的是，CGD患者的PMN摄取经血清调理的念珠菌微生物（相对不可降解的颗粒）的量明显高于正常水平，而且在正常PMN中，叠氮化钠处理也会使其摄取量增加。此外，CGD患者和经叠氮化钠处理的正常PMN与E-IgG形成的玫瑰花结增多。我们发现，这种增强的活性并非Fc受体（FcR）数量增加所致，这是通过单克隆抗FcR抗体的结合情况确定的。在存在H2O2生成系统的情况下，CGD患者的PMN与E-IgG形成玫瑰花结以及摄取E-IgG的能力均被消除。相比之下，外源性H2O2并未改变MPO缺乏症患者的PMN的吞噬活性。这些发现表明，H2O2-MPO-卤化物系统产生的细胞产物会下调正常健康个体PMN的玫瑰花结形成和吞噬活性，但不会下调CGD患者和MPO缺乏症患者的PMN的相关活性。
