Idohou N, Couderc R, Roch-Arveiller M, Tallet F, Giroud J P, Raichvarg D
Laboratoire de Pharmacologie et de Biochimie A, CNRS URA 595, Hôpital Cochin, Paris, France.
Pharmacology. 1993 Jun;46(6):341-5. doi: 10.1159/000139064.
Added to human serum in vitro, RU 41740, an immunomodulating agent extracted from Klebsiella pneumoniae, binds selectively to lipoproteins containing apolipoprotein B (low-density lipoproteins and very-low-density lipoproteins, VLDL) and, at higher concentrations, to lipoproteins containing apolipoprotein A (high-density lipoproteins). The fact that lipoproteins modulate polymorphonuclear neutrophil (PMN) functions led us to suspect that the VLDL-RU 41740 complex might affect PMN functions. In this study, the effect of this complex on PMN superoxide generation was measured in the presence and absence of the classical stimulants formyl-methionyl-leucyl-phenylalanine and phorbol myristate acetate. The VLDL-RU 41740 complex enhanced the stimulating effect of VLDL on quiescent PMN, but not following stimulation with formyl-methionyl-leucyl-phenylalanine. In contrast, it partially counteracted the inhibiting effect exerted by VLDL alone on phorbol myristate acetate stimulation. Such a complex might be formed in vivo during RU 41740 therapy and constitute an important feature in the immunostimulating properties of the drug.
在体外添加到人体血清中时，从肺炎克雷伯菌中提取的免疫调节剂RU 41740会选择性地与含有载脂蛋白B的脂蛋白（低密度脂蛋白和极低密度脂蛋白，VLDL）结合，并且在较高浓度下会与含有载脂蛋白A的脂蛋白（高密度脂蛋白）结合。脂蛋白可调节多形核中性粒细胞（PMN）功能这一事实使我们怀疑VLDL-RU 41740复合物可能会影响PMN功能。在本研究中，在存在和不存在经典刺激物甲酰甲硫氨酰亮氨酰苯丙氨酸和佛波酯肉豆蔻酸酯的情况下，测量了该复合物对PMN超氧化物生成的影响。VLDL-RU 41740复合物增强了VLDL对静止PMN的刺激作用，但在用甲酰甲硫氨酰亮氨酰苯丙氨酸刺激后则没有增强作用。相反，它部分抵消了VLDL单独对佛波酯肉豆蔻酸酯刺激所产生的抑制作用。这种复合物可能在RU 41740治疗期间在体内形成，并构成该药物免疫刺激特性的一个重要特征。
