Hirsch C S, Ellner J J, Russell D G, Rich E A
Department of Medicine, Case Western Reserve University, Cleveland, OH 44106.
J Immunol. 1994 Jan 15;152(2):743-53.
The relative phagocytosis and intracellular fate of Mycobacterium tuberculosis (MTB) (H37Ra) in human alveolar macrophages (AM) and their precursors blood monocytes (MN) was investigated. Uptake of MTB by MN and AM was confirmed by electron microscopy. At an infection ratio of 100:1 (MTB:target cell), the percentage of infected AM and the number of MTB per AM was > MN (p < 0.001, p < 0.0001, respectively). Uptake of MTB was increased by increasing concentrations of serum and decreased in the presence of heat-inactivated serum. Among complement receptors (CR) CR1, CR3, and CR4, the major CR mediating uptake of MTB by MN were CR1 and CR3, whereas for AM, CR4 was the major CR. When MN and AM were infected with MTB and cultured for up to 7 days, AM limited intracellular growth of MTB more effectively than MN as determined by a CFU assay. MTB stimulated production of TNF-alpha by mononuclear phagocytes and by AM > MN (p < 0.007). Pentoxifylline inhibited TNF-alpha production by mononuclear phagocytes and concurrently increased MTB growth (AM > MN). A polyclonal neutralizing antibody to TNF-alpha also increased MTB growth in AM. Thus, AM are more efficient in phagocytosis of MTB than MN, and uptake is mediated through CR4 to a greater extent than CR1 or CR3. The slowed replication of MTB in AM is associated with an increase in TNF-alpha production, and intracellular growth is promoted by pentoxifylline and neutralizing antibody to TNF-alpha. These data suggest that AM may play a prominent and efficient role in the primary defense of the lung in tuberculosis through CR-mediated uptake, predominantly CR4, and TNF-alpha-mediated killing of MTB.
研究了结核分枝杆菌（MTB）（H37Ra）在人肺泡巨噬细胞（AM）及其前体血液单核细胞（MN）中的相对吞噬作用和细胞内命运。通过电子显微镜证实了MN和AM对MTB的摄取。在感染比例为100:1（MTB:靶细胞）时，被感染的AM的百分比和每个AM中的MTB数量均高于MN（分别为p < 0.001，p < 0.0001）。血清浓度增加时，MTB的摄取增加，而在热灭活血清存在下摄取减少。在补体受体（CR）CR1、CR3和CR4中，介导MN摄取MTB的主要CR是CR1和CR3，而对于AM，CR4是主要的CR。当MN和AM感染MTB并培养长达7天时，通过CFU测定法确定，AM比MN更有效地限制了MTB的细胞内生长。MTB刺激单核吞噬细胞和AM产生TNF-α的量大于MN（p < 0.007）。己酮可可碱抑制单核吞噬细胞产生TNF-α，同时增加MTB的生长（AM > MN）。抗TNF-α的多克隆中和抗体也增加了AM中MTB的生长。因此，AM在吞噬MTB方面比MN更有效，并且摄取在更大程度上是通过CR4介导的，而不是CR1或CR3。MTB在AM中复制减慢与TNF-α产生增加有关，己酮可可碱和抗TNF-α中和抗体促进细胞内生长。这些数据表明，AM可能通过CR介导的摄取（主要是CR4）和TNF-α介导的MTB杀伤，在肺结核肺部初级防御中发挥突出而有效的作用。
