Ishizaka S, Takeuchi H, Kimoto M, Kanda S, Saito S
Department of Parasitology, Nara Medical University, Kashihara, Japan.
Int J Immunopharmacol. 1998 Dec;20(12):765-79. doi: 10.1016/s0192-0561(98)00066-6.
The regulatory effects of fosfomycin (FOM) were correlated closely with the multifunction of TGF-beta in the modulation of immune responses in vivo and in vitro. LPS-induced polyclonal IgM and IgG antibody responses were depressed at 3 days after the initial culture and subsequently enhanced at day 10 by FOM or TGF-beta. Neither FOM nor TGF-beta inhibited LPS-induced IgA antibody responses, whereas dexamethasone (DX) reduced polyclonal IgM, IgG and IgA antibody responses wholly. The suppression of antibody responses and Mv1Lu cell proliferation induced by FOM or TGF-beta was partly overcome with soluble TFG-beta receptors (sRIII). Oral, i.v. and i.p. administration of FOM exhibited similar enhanced SRBC-specific antibody responses to that seen after oral administration of TGF-beta. The addition of FOM and latent TGF-beta inhibited the proliferation of Mv1Lu cells, but FOM did not lead to an increase in plasmin activities, which convert latent to active TGF-beta, and further the expression of TGF-beta receptors on the cell surface. In addition, FOM failed to enhance TGF-beta secretion. These findings suggest that immunomodulation of FOM results in increased sensitivity of cells to TGF-beta.
磷霉素（FOM）的调节作用与转化生长因子β（TGF-β）在体内外免疫反应调节中的多功能密切相关。脂多糖（LPS）诱导的多克隆IgM和IgG抗体反应在初始培养后3天受到抑制，随后在第10天被FOM或TGF-β增强。FOM和TGF-β均未抑制LPS诱导的IgA抗体反应，而地塞米松（DX）完全降低了多克隆IgM、IgG和IgA抗体反应。FOM或TGF-β诱导的抗体反应抑制和Mv1Lu细胞增殖可被可溶性TGF-β受体（sRIII）部分克服。口服、静脉注射和腹腔注射FOM后，对绵羊红细胞（SRBC）特异性抗体反应的增强作用与口服TGF-β后相似。FOM和潜伏性TGF-β的添加抑制了Mv1Lu细胞的增殖，但FOM并未导致纤溶酶活性增加，纤溶酶可将潜伏性TGF-β转化为活性TGF-β，进而也未导致细胞表面TGF-β受体表达增加。此外，FOM未能增强TGF-β的分泌。这些发现表明，FOM的免疫调节作用导致细胞对TGF-β的敏感性增加。
