Schlesinger L S
Department of Internal Medicine, University of Iowa, Iowa City 52242.
J Immunol. 1993 Apr 1;150(7):2920-30.
We have examined macrophage receptors that mediate phagocytosis of virulent strains (Erdman and H37Rv) and an attenuated strain (H37Ra) of the intracellular pathogen, Mycobacterium tuberculosis. Adherence of the three strains to monocyte-derived macrophages (MDM) is markedly enhanced (>threefold) in the presence of low levels of fresh serum and requires heat-labile serum components because heat inactivation of serum reduces adherence by 65 +/- 5 to 71 +/- 2%. In the presence and absence of serum, adherence of the three strains to MDM is comparable. By electron microscopy, all bacteria are ingested and reside in phagosomes. C receptors (CR) play an important role in adherence of the three strains to MDM in the presence and absence of serum. mAb against CR1, CR3, and CR4 inhibit adherence of Erdman M. tuberculosis in fresh serum by 75 +/- 3% and inhibit the low level of adherence of Erdman (71 +/- 13%), H37Rv (72 +/- 1%), and H37Ra (64 +/- 14%) M. tuberculosis in the absence of serum. Mannose receptors (MR) play an important role in mediating macrophage adherence of the virulent strains but not the attenuated strain of M. tuberculosis. Preincubation of MDM with soluble mannan or mannose-BSA consistently and significantly inhibits adherence of Erdman and H37Rv (up to 60 +/- 7%) but not H37Ra (0 +/- 1 to 5 +/- 5% enhancement of adherence) in the absence of serum. Down-modulation of macrophage MR on mannan substrates inhibits adherence of Erdman (52 +/- 8%) and H37Rv (55 +/- 6%) but not H37Ra (2 +/- 2% enhancement of adherence). Preincubation of MDM with soluble N-acetylglucosamine-BSA also significantly inhibits adherence of the virulent strains (42 +/- 3%). Preincubation of MDM with glucose-BSA minimally inhibits adherence of the three strains (2 +/- 4 to 12 +/- 5%). Anti-MR antibody inhibits adherence of Erdman (57 +/- 2%) and H37Rv (44 +/- 4%) but not H37Ra (4 +/- 5% enhancement of adherence). Inhibition of adherence of zymosan was comparable with that seen with virulent strains of M. tuberculosis in these studies. Down-modulation of macrophage MR also inhibits adherence of Erdman (48 +/- 9%) and H37Rv (20 +/- 2%) in the presence of serum. Simultaneous blockade of MR and CR does not further inhibit adherence of the virulent M. tuberculosis strains over that seen with blocking CR alone.(ABSTRACT TRUNCATED AT 400 WORDS)
我们研究了介导细胞内病原体结核分枝杆菌的强毒株（埃尔德曼株和H37Rv株）以及减毒株（H37Ra株）吞噬作用的巨噬细胞受体。在低水平新鲜血清存在的情况下，这三种菌株对单核细胞衍生巨噬细胞（MDM）的黏附显著增强（超过三倍），并且需要热不稳定的血清成分，因为血清的热灭活会使黏附降低65±5%至71±2%。在有血清和无血清的情况下，这三种菌株对MDM的黏附相当。通过电子显微镜观察，所有细菌均被摄取并存在于吞噬体中。补体受体（CR）在有血清和无血清的情况下，对这三种菌株与MDM的黏附中发挥重要作用。针对CR1、CR3和CR4的单克隆抗体在新鲜血清中可抑制埃尔德曼结核分枝杆菌的黏附达75±3%，并在无血清时抑制埃尔德曼（71±13%）、H37Rv（72±1%）和H37Ra（64±14%）结核分枝杆菌的低水平黏附。甘露糖受体（MR）在介导结核分枝杆菌强毒株的巨噬细胞黏附中起重要作用，但对减毒株不起作用。在无血清的情况下，用可溶性甘露聚糖或甘露糖 - 牛血清白蛋白预先孵育MDM可持续且显著地抑制埃尔德曼株和H37Rv株的黏附（高达60±7%），但对H37Ra株无抑制作用（黏附增强0±1%至5±5%）。在甘露糖底物上对巨噬细胞MR进行下调可抑制埃尔德曼株（52±8%）和H37Rv株（55±6%）的黏附，但对H37Ra株无抑制作用（黏附增强2±2%）。用可溶性N - 乙酰葡糖胺 - 牛血清白蛋白预先孵育MDM也可显著抑制强毒株的黏附（42±3%）。用葡萄糖 - 牛血清白蛋白预先孵育MDM对这三种菌株的黏附抑制作用最小（2±4%至12±5%）。抗MR抗体可抑制埃尔德曼株（57±2%）和H37Rv株（44±4%）的黏附，但对H37Ra株无抑制作用（黏附增强4±5%）。在这些研究中，酵母聚糖黏附的抑制情况与结核分枝杆菌强毒株相似。在有血清的情况下，对巨噬细胞MR进行下调也可抑制埃尔德曼株（48±9%）和H37Rv株（20±2%）的黏附。同时阻断MR和CR不会比单独阻断CR进一步抑制强毒结核分枝杆菌菌株的黏附。（摘要截取自400字）
