Kimura S, Watanabe A, Takeuchi M, Nagata M, Nakamura K, Harada M
Developmental Research Laboratories, Shionogi & Co. Ltd., Osaka, Japan.
Cell Mol Life Sci. 1998 May;54(5):456-60. doi: 10.1007/s000180050173.
Our previous study revealed that passive cutaneous anaphylaxis (PCA) can be produced in congenitally mast cell-deficient WBB6F1-W/Wv (abbreviated as W/Wv) mice on sensitization with undiluted or slightly diluted allogeneic and xenogeneic antisera but not on sensitization with allogeneic monoclonal immunoglobulin (Ig)E and IgG1 antibodies regardless of the antibody concentration [1]. In view of these findings, the present study was conducted to characterize PCA in this strain from its drug susceptibilities using mast cell-bearing WBB6F1-(+)/+ (abbreviated as +/+) and B6D2F1 mice as references. PCA in W/Wv mice mediated by a low dilution (1:4) of hyperimmune serum to bovine serum albumin of the B6D2F1 mouse origin was markedly suppressed by CV-6209, an antagonist of platelet-activating factor (PAF), but not by antihistamines such as cyproheptadine and oxatomide. In contrast, PCA in +/+ and B6D2F1 mice mediated by a high dilution (1:128) of the anti-serum (virtually by IgG1 antibody) was nearly completely suppressed by antihistamines but not by CV-6209. A remarkable difference between PCA in W/Wv and reference mice was also observed in the susceptibility to monoclonal anti-mouse granulocyte (Gr-1) antibody: PCA in W/Wv mice was potently suppressed by the 1- to 3-day pretreatment with this antibody but that in references was not at all. Putting these present results together with the previous finding that anti-granulocyte antibody greatly reduces circulatory Gr-1+ leukocytes, 1 to 3 days after the treatment [2], it is highly probable that PCA in W/Wv mice mediated by some antibody isotypes other than IgE and IgG1 is produced by PAF mainly released from Gr-1+ cells, while IgG1 antibody-mediated PCA in mast cell-bearing reference mice is evoked by histamine derived from mast cells. PCA homologous to that in W/Wv mice could also be produced in the reference mice on sensitization with undiluted or slightly diluted antiserum, when generalized blueing due to excess IgG1 antibody was removed by the oxatomide treatment before the antigen challenge.
我们之前的研究表明，先天性肥大细胞缺陷的WBB6F1-W/Wv（简称为W/Wv）小鼠在用未稀释或轻度稀释的同种异体和异种抗血清致敏时可产生被动皮肤过敏反应（PCA），但在用同种异体单克隆免疫球蛋白（Ig）E和IgG1抗体致敏时，无论抗体浓度如何均不会产生PCA[1]。鉴于这些发现，本研究以携带肥大细胞的WBB6F1-(+)/+（简称为+/+）和B6D2F1小鼠为对照，通过药物敏感性来表征该品系小鼠的PCA。由低稀释度（1:4）的源自B6D2F1小鼠的抗牛血清白蛋白超免疫血清介导的W/Wv小鼠的PCA，被血小板活化因子（PAF）拮抗剂CV-6209显著抑制，但不受赛庚啶和奥沙米特等抗组胺药的抑制。相比之下，由高稀释度（1:128）的抗血清（实际上由IgG1抗体介导）介导的+/+和B6D2F1小鼠的PCA几乎完全被抗组胺药抑制，但不受CV-6209抑制。在对单克隆抗小鼠粒细胞（Gr-1）抗体的敏感性方面，也观察到W/Wv小鼠和对照小鼠的PCA存在显著差异：用该抗体进行1至3天的预处理可有效抑制W/Wv小鼠的PCA，但对对照小鼠则完全没有影响。将目前的这些结果与之前的发现（即抗粒细胞抗体在治疗后1至3天可大大减少循环中的Gr-1+白细胞）[2]相结合，很有可能由除IgE和IgG1之外的某些抗体同种型介导的W/Wv小鼠的PCA主要由Gr-1+细胞释放的PAF产生，而在携带肥大细胞的对照小鼠中，IgG1抗体介导的PCA是由肥大细胞释放的组胺引起的。在用奥沙米特处理去除抗原攻击前由于过量IgG1抗体导致的全身性发蓝后，用未稀释或轻度稀释的抗血清致敏时，对照小鼠中也可产生与W/Wv小鼠同源的PCA。
