Kikuchi Yoko, Kaplan Allen P
Department of Medicine, Division of Pulmonary and Critical Care, Allergy and Clinical Immunology, Medical University of South Carolina, Charleston 29425, USA.
J Allergy Clin Immunol. 2002 Jan;109(1):114-8. doi: 10.1067/mai.2002.120954.
Histamine release in chronic urticaria is initiated by cross-linking of the alpha subunit of FcepsilonRI by means of IgG antibody, followed by complement activation.
We sought to further elucidate the mechanism by which complement augments histamine release and to assess the role of C5a.
We first quantitated the ability of purified C5a to initiate basophil histamine release and to be inhibited by antibody directed to the C5a receptor. Using this antibody, we quantitated its ability to inhibit histamine release induced by sera from patients with chronic urticaria. We also compared the ability of normal serum, C5-depleted serum, and C5-depleted serum after reconstitution with C5 to augment histamine release by IgG isolated from patients with chronic urticaria.
As the concentration of C5a was increased up to 50 ng/mL, the percentage of histamine release increased and reached a plateau of 40% to 50%; this was inhibited by antibody to the C5a receptor. Preincubation of basophils with antibody to the C5a receptor inhibited basophil histamine release from 15 sera tested, with a range of 4% to 39%. Histamine release caused by patient IgG was augmented when normal serum was added but not when C5-depleted serum was substituted for normal serum. Augmentation of histamine release by patient IgG was again obtained when C5-depleted serum was reconstituted with C5.
Our conclusion is that pathogenic IgG cross-links the IgE receptor directly to cause histamine release, and activation is augmented by complement. C5a is the complement agonist that is responsible for the augmented histamine release.
慢性荨麻疹中的组胺释放是由IgG抗体通过交联FcepsilonRI的α亚基引发的，随后是补体激活。
我们试图进一步阐明补体增强组胺释放的机制，并评估C5a的作用。
我们首先定量纯化的C5a引发嗜碱性粒细胞组胺释放以及被针对C5a受体的抗体抑制的能力。使用该抗体，我们定量其抑制慢性荨麻疹患者血清诱导的组胺释放的能力。我们还比较了正常血清、C5缺陷血清以及用C5重构后的C5缺陷血清增强慢性荨麻疹患者分离的IgG组胺释放的能力。
随着C5a浓度增加至50 ng/mL，组胺释放百分比增加并达到40%至50%的平台期；这被针对C5a受体的抗体抑制。用针对C5a受体的抗体预孵育嗜碱性粒细胞可抑制15份受试血清的嗜碱性粒细胞组胺释放，范围为4%至39%。添加正常血清时患者IgG引起的组胺释放增强，但用C5缺陷血清替代正常血清时则不然。当用C5重构C5缺陷血清时，患者IgG引起的组胺释放再次增强。
我们的结论是，致病性IgG直接交联IgE受体以引起组胺释放，补体可增强激活作用。C5a是导致组胺释放增强的补体激动剂。
