Mauel J, Van Pham T, Kreis B, Bauer J
Université de Lausanne, Institut de Biochimie, Epalinges, Switzerland.
Int J Immunopharmacol. 1989;11(6):637-45. doi: 10.1016/0192-0561(89)90149-5.
Peritoneal and bone marrow-derived macrophages of the C57BL/6 and DBA/2 mouse strains were exposed in vitro to increasing concentrations of the bacterial lysate Broncho-Vaxom (BV), in the presence or absence of macrophage-activating factor (MAF)-rich media. Two metabolic pathways and two functional activities of the macrophages were studied. First, oxidative metabolism was found to increase sharply in macrophages incubated with BV, as measured by the catabolism of glucose via the hexose monophosphate shunt pathway, and by the production of the superoxide anion (O2-). Both effects were further increased by co-stimulation of macrophages with MAF. Second, exposure to BV together with MAF (or with recombinant murine interferon-gamma) led to acquisition by macrophages of the capacity to destroy the intracellular parasite Leishmania enriettii; such activated macrophages were also lytic towards P815 mastocytoma indicator target cells. These cytotoxic properties failed to develop in the absence of MAF. The BV-dependent increase in metabolic and functional activities was of the same magnitude as that induced by incubation of macrophages with 10 ng/ml of bacterial lipopolysaccharide (LPS). Residual contamination of BV by endotoxin was however much lower. In addition, polymyxin B, a LPS inhibitor, blocked the effect of LPS without significantly affecting macrophage stimulation by BV. These experiments indicate that BV can markedly stimulate macrophage metabolic and functional parameters that are important for host defense against pathogens and tumors.
将C57BL/6和DBA/2小鼠品系的腹膜巨噬细胞和骨髓来源的巨噬细胞,在有或无富含巨噬细胞激活因子(MAF)的培养基存在的情况下,于体外暴露于浓度不断增加的细菌裂解物支气管疫苗(BV)中。研究了巨噬细胞的两条代谢途径和两种功能活性。首先,发现与BV一起孵育的巨噬细胞的氧化代谢急剧增加,这通过己糖磷酸分流途径的葡萄糖分解代谢以及超氧阴离子(O2-)的产生来衡量。巨噬细胞与MAF共同刺激可进一步增强这两种效应。其次,将BV与MAF(或与重组小鼠干扰素-γ)一起暴露,可使巨噬细胞获得破坏细胞内寄生虫恩氏利什曼原虫的能力;这种活化的巨噬细胞对P815肥大细胞瘤指示靶细胞也具有细胞溶解作用。在没有MAF的情况下,这些细胞毒性特性无法形成。BV依赖性的代谢和功能活性增加与巨噬细胞与10 ng/ml细菌脂多糖(LPS)孵育所诱导的增加幅度相同。然而,BV中内毒素的残留污染要低得多。此外,LPS抑制剂多粘菌素B可阻断LPS的作用,而不会显著影响BV对巨噬细胞的刺激。这些实验表明,BV可显著刺激巨噬细胞的代谢和功能参数,这些参数对于宿主抵御病原体和肿瘤至关重要。