Blussé van Oud Alblas A, van der Linden-Schrever B, van Furth R
J Exp Med. 1981 Aug 1;154(2):235-52. doi: 10.1084/jem.154.2.235.
This report gives a quantitative description of the kinetics of the pulmonary macrophages and their direct precursors during the acute inflammatory reaction in the lungs induced by intravenous injection of heat-killed bacillus Calmette-Guérin (BCG) into specific-pathogen-free mice. After BCG injection, the total number of pulmonary macrophages isolated by lavage and subsequent enzyme digestion of lung tissue increased to 225% of normal within 12 h and, after a minor decrease, rose to a maximum of 250% of normal at 96 h, followed by a decrease to 150% at 144 h, the end of the observation period. The number of circulating monocytes doubled in the first 48 h and stayed close to that level. In vivo and in vitro labeling with [3H]-thymidine showed that an influx of monocytes transforming into pulmonary macrophages was mainly responsible for the population increase. A temporary increase in the number of locally dividing pulmonary macrophages--manifested by an increased in vitro labeling index, reaching a maximum of 9.6% 72 h after BCG injection--made a minor contribution to the population increase. All pulmonary macrophages were classified according to morphological criteria as alveolar-macrophage-like (AML) or non-alveolar-macrophage-like (NAML), and their respective characteristics were established. The in vivo labeling data showed NAML to represent exudate macrophages derived from circulating monocytes entering the interstitial tissue, and these cells changed morphologically into AML upon entering the alveolar hypophase. This mechanism was confirmed by the finding that the interstitially deposited BCG were found first inside NAML and later in AML. The in vivo labeling data showed that local production was mainly a result of division of macrophages that were morphologically identical with normal alveolar macrophages. The former cells, however, derived most probably recently from the circulation, because the turnover of the total population was very high before local macrophage production became maximal. In mice treated with HC before the injection of BCG, this population increase was absent, because of virtual abolition of the initial monocyte influx and absence of the increased local production of macrophages. Calculations showed that the monocyte influx in the first 48 h amounted to approximately 4 x 10(6) cells, i.e., eight times that found in the normal steady state, and that the efflux of pulmonary macrophages in that period amounted to approximately 3.5 x 10(6) cells, i.e., seven times the normal efflux. The local production over the total period of 144 h was only three times that found normally. The results of these quantitative studies show that the increase of the pulmonary macrophage population during an acute inflammation is brought about mainly by monocyte influx and to a minor extent by a temporary increased local production of macrophages. Disposal of interstitially deposited BCG occurred by phagocytosis by local macrophages and the subsequent efflux of the latter.
本报告定量描述了在无特定病原体小鼠静脉注射热灭活卡介苗（BCG）诱导的肺部急性炎症反应期间，肺巨噬细胞及其直接前体细胞的动力学变化。注射BCG后，通过灌洗分离并随后对肺组织进行酶消化得到的肺巨噬细胞总数在12小时内增加至正常水平的225%，经过轻微下降后，在96小时时升至正常水平的250%的最大值，随后在观察期结束时的144小时降至150%。循环单核细胞数量在前48小时内翻倍，并维持在该水平附近。用[3H] - 胸腺嘧啶核苷进行体内和体外标记显示，单核细胞流入并转变为肺巨噬细胞是细胞数量增加的主要原因。局部增殖的肺巨噬细胞数量暂时增加——表现为体外标记指数增加，在注射BCG后72小时达到最大值9.6%——对细胞数量增加的贡献较小。所有肺巨噬细胞根据形态学标准分为肺泡巨噬细胞样（AML）或非肺泡巨噬细胞样（NAML），并确定了它们各自的特征。体内标记数据显示，NAML代表源自进入间质组织的循环单核细胞的渗出巨噬细胞，这些细胞在进入肺泡后期时形态上转变为AML。间质中沉积的BCG首先在NAML内被发现，随后在AML内被发现，这一发现证实了这一机制。体内标记数据显示，局部产生主要是形态上与正常肺泡巨噬细胞相同的巨噬细胞分裂的结果。然而，前一种细胞很可能最近来自循环系统，因为在局部巨噬细胞产生达到最大值之前，细胞总数的周转率非常高。在注射BCG前用氢化可的松（HC）处理的小鼠中，由于最初的单核细胞流入几乎完全被消除且巨噬细胞的局部产生没有增加，所以细胞数量没有增加。计算表明，前48小时内单核细胞流入量约为4×10⁶个细胞，即正常稳态下的8倍，该时期肺巨噬细胞流出量约为3.5×10⁶个细胞，即正常流出量的7倍。144小时整个期间的局部产生量仅为正常情况下的3倍。这些定量研究结果表明，急性炎症期间肺巨噬细胞数量的增加主要是由单核细胞流入引起的，局部巨噬细胞产生量的暂时增加对其影响较小。间质中沉积的BCG通过局部巨噬细胞的吞噬作用以及后者随后的流出而被清除。
