Ross G D, Thompson R A, Walport M J, Springer T A, Watson J V, Ward R H, Lida J, Newman S L, Harrison R A, Lachmann P J
Blood. 1985 Oct;66(4):882-90.
Three children from two unrelated families had a history of recurrent bacterial infections, and their neutrophils were shown to have deficient phagocytic and respiratory responses and possible deficiencies in chemotaxis or adherence. Their neutrophils were strikingly deficient in the ability to ingest or give a respiratory burst in response to unopsonized bakers' yeast or zymosan (Z). Tests for neutrophil and monocyte CR1 (C3b/iC3b receptor) and CR3 (iC3b receptor) demonstrated rosettes with both EC3b and EC3bi. However, EC3bi were bound only to CR1, and not to CR3, because EC3bi rosettes were inhibited completely by anti-CR1. Neutrophils, monocytes, and natural killer (NK) cells also did not fluorescence stain with monoclonal antibodies specific for the alpha-chain of CR3 (anti-Mac-1, anti-Mol, OKM1, and MN-41). Quantitation of C receptors with 125I monoclonal anti-CR1 and anti-CR3 indicated that neutrophils from each patient expressed normal amounts of CR1 per cell but less than 10% of the normal amount of CR3. Examination of neutrophils by sodium dodecyl sulfate-polyacrylamide gel electrophoresis demonstrated that a normal glycoprotein of approximately 165,000 daltons was missing. Immunoblotting of these gels indicated that the missing band was the alpha-chain of CR3. Subsequent analysis of all three patients' cells also demonstrated a deficiency of LFA-1 alpha-chain and the common beta-chain that is shared by the CR3/LFA-1/p150,95 membrane antigen family. The deficiency of LFA-1 probably explained the absent NK cell function, as normal NK cell activity is inhibited by anti-LFA-1 but not by anti-CR3. The reduced phagocytic and respiratory responses to Z were probably due to CR3 deficiency, because treatment of normal neutrophils with anti-CR3, but not anti-FLA-1, inhibits responses to Z by 80% to 90%. Ingestion of Staphylococcus epidermidis by normal neutrophils was shown to be partially inhibited by monoclonal antibodies to the alpha-chain of either CR3 or LFA-1, and monoclonal antibody to the common beta-chain inhibited ingestion by 75%. Thus, both CR3 and LFA-1 may have previously unrecognized functions as phagocyte receptors for bacteria. The absence of this type of nonimmune recognition of bacteria by these children's neutrophils may be one of the reasons for their increased susceptibility to bacterial infections.
来自两个无亲缘关系家庭的三名儿童有反复细菌感染史，他们的中性粒细胞显示出吞噬和呼吸反应缺陷，以及趋化或黏附方面可能存在的缺陷。他们的中性粒细胞在摄取或对未调理的面包酵母或酵母聚糖（Z）产生呼吸爆发的能力上明显不足。对中性粒细胞和单核细胞的CR1（C3b/iC3b受体）和CR3（iC3b受体）的检测显示，它们与EC3b和EC3bi均形成花环。然而，EC3bi仅与CR1结合，而不与CR3结合，因为EC3bi花环被抗CR1完全抑制。中性粒细胞、单核细胞和自然杀伤（NK）细胞也不能被针对CR3α链的单克隆抗体（抗Mac-1、抗Mol、OKM1和MN-41）荧光染色。用125I单克隆抗CR1和抗CR3对C受体进行定量分析表明，每位患者的中性粒细胞每个细胞表达的CR1量正常，但CR3量不到正常量的10%。通过十二烷基硫酸钠-聚丙烯酰胺凝胶电泳对中性粒细胞进行检测发现，一种约165,000道尔顿的正常糖蛋白缺失。对这些凝胶进行免疫印迹分析表明，缺失的条带是CR3的α链。随后对所有三名患者的细胞进行分析还发现，LFA-1α链以及CR3/LFA-1/p150,95膜抗原家族共有的β链存在缺陷。LFA-1的缺陷可能解释了NK细胞功能的缺失，因为正常的NK细胞活性可被抗LFA-1抑制，而不能被抗CR3抑制。对Z的吞噬和呼吸反应降低可能是由于CR3缺陷，因为用抗CR3而非抗FLA-1处理正常中性粒细胞可使对Z的反应抑制80%至90%。正常中性粒细胞对表皮葡萄球菌的摄取显示，针对CR3或LFA-1α链的单克隆抗体可部分抑制其摄取，而针对共同β链的单克隆抗体可使摄取抑制75%。因此，CR3和LFA-1可能都具有以前未被认识到的作为细菌吞噬细胞受体的功能。这些儿童的中性粒细胞缺乏这种对细菌的非免疫识别可能是他们易患细菌感染的原因之一。
