Langermans J A, van der Hulst M E, Nibbering P H, van der Meide P H, van Furth R
Department of Infectious Diseases, University Hospital, Leiden, The Netherlands.
Immunology. 1992 Nov;77(3):354-61.
In the present study the effects of intravenous administration of recombinant interferon-gamma (IFN-gamma) on both the proliferation of Listeria monocytogenes in the liver and spleen of mice and the listericidal activity of their peritoneal macrophages were investigated. A single intravenous injection of 1 x 10(6) U or three injections of 2 x 10(5) U recombinant IFN-gamma (rIFN-gamma) induced optimal activation of resident and exudate peritoneal macrophages, as judged by their ability to inhibit the intracellular proliferation of Toxoplasma gondii and their enhanced release of H2O2 and NO2-. The rate of intracellular killing of L. monocytogenes by the rIFN-gamma-activated resident and exudate macrophages was not higher than that by resident macrophages. Addition of 10 ng lipopolysaccharides (LPS) to the rIFN-gamma also did not enhance the bactericidal activity of the activated peritoneal macrophages. The decrease in the number of L. monocytogenes in the peritoneal cavity of mice that had received an i.p. injection of 1 x 10(4) U rIFN-gamma was similar to that in control mice. Intravenous administration of 1 x 10(5) rIFN-gamma activated cells in the liver, as indicated by the increased expression of Ia antigen, and reduced the rate of proliferation of L. monocytogenes in the liver relative to that in control mice when 0.1 LD50 or 1 LD50 L. monocytogenes were injected. However, when 10 LD50 L. monocytogenes were administered there was no effect on their proliferation. The number of L. monocytogenes found initially in the spleen of rIFN-gamma-treated mice was 20-30% of that in the spleen of control mice, but the rate of proliferation of L. monocytogenes was not reduced. These divergent results for the proliferation of L. monocytogenes in the liver, spleen and peritoneal cavity indicate that cells other than macrophages and/or as yet unknown local factors play an important role in the listericidal activity.
在本研究中,研究了静脉注射重组干扰素-γ(IFN-γ)对小鼠肝脏和脾脏中单核细胞增生李斯特菌增殖以及其腹腔巨噬细胞杀菌活性的影响。单次静脉注射1×10⁶U或三次注射2×10⁵U重组IFN-γ(rIFN-γ)可诱导驻留和渗出腹腔巨噬细胞的最佳活化,这可通过它们抑制刚地弓形虫细胞内增殖的能力以及增强的H₂O₂和NO₂⁻释放来判断。rIFN-γ激活的驻留和渗出巨噬细胞对单核细胞增生李斯特菌的细胞内杀伤率并不高于驻留巨噬细胞。向rIFN-γ中添加10 ng脂多糖(LPS)也未增强活化腹腔巨噬细胞的杀菌活性。腹腔注射1×10⁴U rIFN-γ的小鼠腹腔中单核细胞增生李斯特菌数量的减少与对照小鼠相似。静脉注射1×10⁵rIFN-γ可激活肝脏中的细胞,如Ia抗原表达增加所示,并且当注射0.1 LD₅₀或1 LD₅₀单核细胞增生李斯特菌时,相对于对照小鼠,可降低肝脏中单核细胞增生李斯特菌的增殖率。然而,当给予10 LD₅₀单核细胞增生李斯特菌时,对其增殖没有影响。在rIFN-γ处理的小鼠脾脏中最初发现的单核细胞增生李斯特菌数量是对照小鼠脾脏中的20%-30%,但单核细胞增生李斯特菌的增殖率并未降低。单核细胞增生李斯特菌在肝脏、脾脏和腹腔中增殖的这些不同结果表明,除巨噬细胞外的其他细胞和/或尚未知的局部因素在杀菌活性中起重要作用。