Chevance L G, Etiévant M
J Pharmacol. 1986 Oct-Dec;17(4):676-85.
A peptide of simple chemical structure has demonstrated its efficiency in preventing the large cellular destruction that locally activated complement produced on the ciliary epithelium of the respiratory tract. Previously (1980), it was demonstrated by the authors that these cellular destructions after sensitization of the epithelium was due to the local activation of the complement (alternate pathway) by immune complexes with secretory IgA. The cellular protection afforded by Naaga was demonstrated by the persistance of a normal ciliary beating when the sensitized mucosa is in contact with the antigen; by electron microscopic studies both in transmission and scanning E.M. contrasting with the complete cellular destructions of the epithelium which appear obvious. The protection appear complete when Naaga (56 mM) is present in the testing solution (or instillated before the test). By in vitro human complement studies; study of the cytolytic sequence inhibition for the classical pathway 1,5.10(-3) M of Naaga produces a 50% inhibition of 1 H50 hemolytic unit. For the alternate pathway, the same inhibition is observed with 1,75.10(-3) M of Naaga; by two-dimensions immuno-electrophoresis: a dilution of 1/2 of C3 in Naaga reduced to 1/10 of its normal value the C3b profile; the "Rockets" technique demonstrated that the same 1/2 dilution of Naaga in complement prevents the clivage of factor B and that this peptide acts by inhibition of the alternate C3 convertase formation (see illustrations). If we consider the subject of this study i.e. the upper respiratory tract mucosa and knowing the physiopathological importance of the muco ciliary complex in preventing dust, microbs and other particulate foreign materiel to penetrate the epithelium, the therapeutic importance of such a simple non toxic and unharmful chemical compound must be stressed.
一种化学结构简单的肽已证明其在预防局部激活补体对呼吸道纤毛上皮产生的大量细胞破坏方面具有有效性。此前(1980年),作者证明上皮致敏后这些细胞破坏是由于免疫复合物与分泌型IgA局部激活补体(替代途径)所致。当致敏黏膜与抗原接触时,正常的纤毛摆动持续存在,证明了那加肽(Naaga)提供的细胞保护作用;通过透射电子显微镜和扫描电子显微镜研究,与明显出现的上皮细胞完全破坏形成对比。当测试溶液中存在那加肽(56 mM)(或在测试前滴注)时,保护作用似乎是完全的。通过体外人体补体研究;对经典途径的细胞溶解序列抑制研究表明,1,5.10(-3) M的那加肽可产生50%的1 H50溶血单位抑制作用。对于替代途径,1,75.10(-3) M的那加肽可观察到相同的抑制作用;通过二维免疫电泳:在那加肽中C3稀释至1/2可将C3b图谱降低至其正常值的1/10;“火箭”技术表明,在补体中相同的1/2那加肽稀释液可防止因子B的裂解,且该肽通过抑制替代C3转化酶的形成发挥作用(见图例)。如果我们考虑本研究的主题,即上呼吸道黏膜,并了解黏液纤毛复合体在防止灰尘、微生物和其他颗粒性异物穿透上皮方面的生理病理重要性,那么必须强调这种简单无毒无害的化合物的治疗重要性。