[A peptide (a magnesium salt of N-acetyl (alpha, beta)-aspartyl-glutamic acid). Demonstration of the protection against local cellular destruction induced by in situ complement activation].

Journal de pharmacologie Pub Date : 1986-10-01
L G Chevance, M Etiévant
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Abstract

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.

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一种肽(n -乙酰(α, β)-天冬氨酸-谷氨酸的镁盐)。对由原位补体激活引起的局部细胞破坏的保护论证]。
一种化学结构简单的肽在防止呼吸道纤毛上皮局部激活补体产生的大细胞破坏方面具有效率。先前(1980年),作者证明了上皮致敏后的这些细胞破坏是由于具有分泌IgA的免疫复合物局部激活补体(替代途径)。当致敏粘膜与抗原接触时,Naaga提供的细胞保护可以通过持续正常的纤毛跳动来证明;透射电镜和扫描电镜显示,上皮细胞明显破坏。当Naaga (56 mM)存在于测试溶液中(或在测试前注入)时,保护就会完成。通过体外人体补体研究;Naaga经典途径1,5.10(-3)M的细胞溶解序列抑制研究,对1 H50溶血单位产生50%的抑制作用。对于替代途径,同样的抑制作用观察到1,75.10(-3)M的Naaga;通过二维免疫电泳:在Naaga中稀释1/2的C3,将C3b剖面降低到正常值的1/10;“火箭”技术表明,补体中相同的1/2 Naaga稀释可以阻止因子B的切割,并且该肽通过抑制替代C3转化酶的形成而起作用(见插图)。如果我们考虑到本研究的对象是上呼吸道粘膜,并且知道粘膜纤毛复合物在防止灰尘、微生物和其他颗粒状外来物质穿透上皮中的生理病理重要性,那么必须强调这种简单无毒无害的化合物的治疗重要性。
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