Salem M L, Matsuzaki G, Madkour G A, Nomoto K
Department of Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
Int J Immunopharmacol. 1999 Aug;21(8):481-97. doi: 10.1016/s0192-0561(99)00027-2.
Mice treated with a contraceptive dose of beta-estradiol (E2) demonstrated changes in their macrophage (Mphi) number and functions. While E2 increased and decreased the Mphi number in PBMC and PEC respectively, it enhanced the in vitro phagocytosis of FITC-labeled beads by both cells. E2 treatment also enhanced the phagocytic function of Mphi as assessed by the in vivo carbon clearance assay. In contrast, the in vitro intracellular killing function of adherent cells in peritoneal exudate cells (PEC) against Listeria monocytogenes decreased after E2 treatment. In line with the decrease in the intracellular killing function, the E2-treated mice showed an impaired protection against L. monocytogenes infection. To clarify the mechanism of the E2-mediated suppression of the protective response against L. monocytogenes infection, we next analyzed the cytokine expression by PEC in E2-treated L. monocytogenes-infected mice. On day 5 of the infection, the expression of IL-12, TNF-alpha and IL-10 by adherent PEC from the E2-treated mice was lower than that from the control-infected mice. The decrease in the cytokine expression by adherent PEC of E2-treated mice coincided with the decrease of IFN-gamma expression, and the increase in the IL-4, IL-10 and TGF-beta expressions by non-adherent PEC. These results revealed two aspects of the effects of E2 on Mphi. Even though E2 was found to enhance Mphi phagocytosis, the anti-bacterial function was suppressed. This suppression may be mediated by the inhibition of both IL-12 and TNF-alpha which play important roles in the protective response against intracellular bacteria.
用避孕剂量的β-雌二醇（E2）处理的小鼠巨噬细胞（Mphi）数量和功能出现了变化。虽然E2分别增加和减少了外周血单核细胞（PBMC）和腹腔渗出细胞（PEC）中的Mphi数量，但它增强了这两种细胞对异硫氰酸荧光素（FITC）标记珠子的体外吞噬作用。通过体内碳清除试验评估，E2处理还增强了Mphi的吞噬功能。相反，E2处理后，腹腔渗出细胞（PEC）中贴壁细胞对单核细胞增生李斯特菌的体外细胞内杀伤功能下降。与细胞内杀伤功能的下降一致，经E2处理的小鼠对单核细胞增生李斯特菌感染的保护作用受损。为了阐明E2介导的对单核细胞增生李斯特菌感染的保护性反应抑制机制，接下来我们分析了E2处理的单核细胞增生李斯特菌感染小鼠中PEC的细胞因子表达。在感染的第5天，来自E2处理小鼠的贴壁PEC中白细胞介素-12（IL-12）、肿瘤坏死因子-α（TNF-α）和白细胞介素-10（IL-10）的表达低于对照感染小鼠。E2处理小鼠贴壁PEC中细胞因子表达的下降与干扰素-γ（IFN-γ）表达的下降以及非贴壁PEC中IL-4、IL-10和转化生长因子-β（TGF-β）表达的增加相一致。这些结果揭示了E2对Mphi作用的两个方面。尽管发现E2增强了Mphi的吞噬作用，但其抗菌功能受到抑制。这种抑制可能是由对IL-12和TNF-α的抑制介导的，它们在针对细胞内细菌的保护性反应中起重要作用。
