Khare S, Bhutani L K, Rao D N
Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India.
Mol Cell Biochem. 1997 Jun;171(1-2):1-10. doi: 10.1023/a:1006861509742.
Tuftsin, a tetrapeptide (Thr-Lys-Pro-Arg) is known to potentiate the immunogenic activity of antigen-fed macrophages. The present study describes the mechanism of action of tuftsin in leprosy patients throughout the spectrum of the disease in vitro as a function of culture age in terms of (A) involvement of second messengers cAMP, cGMP and [Ca2+]i and (B) number of tuftsin binding sites/and their relative affinities on the monocytes/macrophages. There is apparently no direct involvement of either cAMP or cGMP while comparing the stimulated and unstimulated cultures during in vitro differentiation of monocytes (days 1, 3 and 7) or with the spectrum of the disease. Inhibition of superoxide anion release either by verapamil or with Quin 2 clearly demonstrated the involvement of [Ca2+]i as a second messenger during activation of monocytes/macrophages with tuftsin. Scatchard analysis of radiolabelled tuftsin binding data showed only one type of tuftsin receptor (low affinity) on BL/ LL monocytes/macrophages and normal and BT/TT cultures showed a gradual change in receptor number and affinities (low to high) with the maturation of monocytes to macrophages in contrast to BL/LL groups which displayed significantly less number of receptors. This study elicits a model which depicts that the biological responses/metabolic functions of early monocytes of normal and BT/TT gradually increase with the age of the culture till day 3 and tapers off thereafter in the older (day 7) cultures, whereas the monocytes/macrophages of BL/LL group are metabolically active only on day 1. The present study thereby implies that the clearance of leprosy bacilli from lepromatous leprosy lesions as a consequence of local or systemic immunotherapy (in the present study, the macrophage modulation by tuftsin) depends on the influx of new competent macrophages, rather than the local activation of resident lepromatous macrophages.
促吞噬素是一种四肽（苏氨酸 - 赖氨酸 - 脯氨酸 - 精氨酸），已知它能增强摄取抗原的巨噬细胞的免疫原活性。本研究描述了促吞噬素在体外对各型麻风病患者的作用机制，该机制是培养时间的函数，具体涉及（A）第二信使环磷酸腺苷（cAMP）、环磷酸鸟苷（cGMP）和细胞内钙离子浓度（[Ca2+]i），以及（B）促吞噬素结合位点的数量及其在单核细胞/巨噬细胞上的相对亲和力。在比较单核细胞体外分化过程中（第1、3和7天）或不同类型麻风病患者的刺激和未刺激培养物时，cAMP或cGMP显然没有直接参与。维拉帕米或喹啉2抑制超氧阴离子释放，清楚地证明了在促吞噬素激活单核细胞/巨噬细胞过程中，[Ca2+]i作为第二信使发挥了作用。对放射性标记的促吞噬素结合数据进行Scatchard分析表明，在瘤型/界线类偏瘤型（BL/LL）单核细胞/巨噬细胞上只有一种促吞噬素受体（低亲和力），而正常以及结核样型/界线类偏结核样型（BT/TT）培养物显示，随着单核细胞成熟为巨噬细胞，受体数量和亲和力（从低到高）逐渐变化，与之形成对比的是，BL/LL组的受体数量明显较少。本研究得出了一个模型，该模型表明正常以及BT/TT型早期单核细胞的生物学反应/代谢功能随着培养时间延长至第3天逐渐增强，之后在较老的（第7天）培养物中逐渐减弱，而BL/LL组的单核细胞/巨噬细胞仅在第1天具有代谢活性。因此，本研究表明，局部或全身免疫治疗（在本研究中为促吞噬素对巨噬细胞的调节）导致瘤型麻风病病变中麻风杆菌的清除，取决于新的有功能的巨噬细胞的流入，而不是局部驻留的瘤型巨噬细胞的激活。
