Carlone N A, Cuffini A M, Tullio V, Cavallo G
Institute of Microbiology, University of Turin, Italy.
J Chemother. 1991 Jan;3 Suppl 1:98-104.
The goal of antimicrobial therapy is to eliminate invading bacteria both in the extracellular and intracellular environment. Thus, recent work has focused on the ability of various antibiotics to enter phagocytic cells and kill intracellular pathogens, since bacteria which survive within phagocytes may often produce prolonged or recurrent infections. In the last ten years the antibiotic modulation of phagocytic cell functions has become the subject of our major investigational activity. Taking into account that entry of antibiotics into phagocytes is necessary for activity against intracellular organisms, we examined the uptake of 11 radiolabelled antibiotics by macrophages. Penicillins and cephalosporins were taken up poorly by phagocytes. Teicoplanin was efficiently concentrated by macrophages, achieving intracellular concentrations higher than those in the surrounding extracellular medium. Roxithromycin was more markedly accumulated within phagocytes than was erythromycin, depending upon an active transport mechanism. Antitubercular drugs were concentrated approximately twofold in the macrophages. Besides, since antibiotics that act on phagocytosed bacteria have clinical advantages, we evaluated the direct action of the above mentioned drugs on the macrophage, by determining their interference with its functions or their potentiation of both phagocytosis and killing of bacteria.
抗菌治疗的目标是清除细胞外和细胞内环境中的入侵细菌。因此，近期的研究工作聚焦于各种抗生素进入吞噬细胞并杀死细胞内病原体的能力，因为存活于吞噬细胞内的细菌往往会导致持续性或复发性感染。在过去十年中，抗生素对吞噬细胞功能的调节已成为我们主要研究活动的主题。考虑到抗生素进入吞噬细胞是对抗细胞内病原体活性所必需的，我们检测了巨噬细胞对11种放射性标记抗生素的摄取情况。青霉素和头孢菌素被吞噬细胞摄取的情况较差。替考拉宁能被巨噬细胞有效浓缩，细胞内浓度高于周围细胞外培养基中的浓度。罗红霉素在吞噬细胞内的积累比红霉素更显著，这依赖于一种主动转运机制。抗结核药物在巨噬细胞中的浓度约为两倍。此外，由于作用于被吞噬细菌的抗生素具有临床优势，我们通过测定它们对巨噬细胞功能的干扰或对吞噬作用和细菌杀伤的增强作用，评估了上述药物对巨噬细胞的直接作用。
