Spangrude G J, Sacchi F, Hill H R, Van Epps D E, Daynes R A
J Immunol. 1985 Dec;135(6):4135-43.
The cells of the mammalian immune system possess special migratory properties within their in vivo environment, a surveillance characteristic that is thought to be important in the protection of the organism from transformants and exogenous pathogens. Pertussis toxin (PT) has been shown to disrupt the intensity of this process by seriously affecting lymphocyte recirculation in vivo. The mechanisms responsible for this inhibition were investigated by using the in vitro model systems of polymorphonuclear leukocyte and lymphocyte chemotaxis. The type of inhibition that was observed in these in vitro assay systems was quite similar to that observed in vivo, because PT could depress chemotaxis in vitro as well as the accumulation of radiolabeled lymphocytes and neutrophils within a peripheral site of inflammation in vivo. The alterations in neutrophil motility were found to be associated with a stimulus-specific inhibition of the triggering of superoxide anion generation and lysosomal secretion. Some inhibition of neutrophil adherence to plastic surfaces was also observed, most notably after augmentation of adherence with the chemoattractant fMLP. The observed alterations in cellular function after PT treatment occurred in the absence of defects in chemoattractant binding to the neutrophil cell surface, or of membrane potential changes stimulated by ligand binding. The effect of PT in this system was found to be associated with an abnormality in the regulation of intracellular free calcium, suggesting that the substrate for PT in neutrophils is involved in the regulation of calcium ion channels.
哺乳动物免疫系统的细胞在其体内环境中具有特殊的迁移特性，这种监测特性被认为对于保护机体免受转化细胞和外源病原体的侵害非常重要。百日咳毒素（PT）已被证明会通过严重影响体内淋巴细胞再循环来破坏这一过程的强度。通过使用多形核白细胞和淋巴细胞趋化性的体外模型系统来研究这种抑制作用的机制。在这些体外测定系统中观察到的抑制类型与在体内观察到的非常相似，因为PT既能在体外抑制趋化性，也能抑制体内炎症外周部位放射性标记淋巴细胞和中性粒细胞的聚集。发现中性粒细胞运动性的改变与超氧阴离子生成触发和溶酶体分泌的刺激特异性抑制有关。还观察到中性粒细胞对塑料表面的黏附受到一定抑制，尤其是在用趋化剂fMLP增强黏附后。在PT处理后观察到的细胞功能改变发生时，趋化剂与中性粒细胞细胞表面的结合没有缺陷，或者配体结合刺激的膜电位变化也没有缺陷。发现PT在该系统中的作用与细胞内游离钙调节异常有关，这表明中性粒细胞中PT的底物参与钙离子通道的调节。
