Terashima T, Klut M E, English D, Hards J, Hogg J C, van Eeden S F
University of British Columbia Pulmonary Research Laboratory, St. Paul's Hospital, Vancouver, British Columbia, Canada.
Am J Respir Cell Mol Biol. 1999 Jan;20(1):171-7. doi: 10.1165/ajrcmb.20.1.3276.
Studies from our laboratory have shown that chronic cigarette smoke exposure causes a neutrophilia associated with a shortening of the mean transit time of polymorphonuclear leukocytes (PMN) though the postmitotic pool of the marrow. The present study was designed to test the hypothesis that PMN newly released from bone marrow by smoke exposure preferentially sequestered in pulmonary microvessels. The thymidine analogue 5'-bromo-2'-deoxyuridine (BrdU) was used to label dividing PMN in the marrow of rabbits; their appearance in the circulation was measured using immunocytochemistry, and their sequestration in lung tissue was determined using standard morphometric techniques. Animals exposed to 11 d of cigarette smoke (n = 6) compared with sham-exposed control animals (n = 4) showed no increase in circulating PMN counts but showed an increase in both the percentage of band cells (smoking, 9.8 +/- 1.1% versus control, 5.5 +/- 0.9%; P < 0.05) and BrdU-labeled PMN (PMNBrdU) in the circulation (smoking, 10.8 +/- 0.6% versus control, 7.5 +/- 0.3%; P < 0.05). There were more PMN sequestered in the lungs of smoke-exposed animals (51.7 +/- 3.4 x 10(7)/ml tissue) than in those of control animals (25.1 +/- 1.8 x 10(7)/ ml tissue) (P < 0.05) and a higher percentage of these cells were PMNBrdU (smoking, 16.9 +/- 2. 3% versus control, 9.6 +/- 0.4%; P < 0.05). The percentage of PMNBrdU in the gravity-independent regions (11.7 +/- 1.9%) of the lung was higher than gravity-dependent regions (7.8 +/- 1.8%) in the smoke-exposure group (P < 0.05). Transmission electron microscopy showed pulmonary capillary endothelial damage with adherent PMN in the smoke-exposure group. We conclude that younger PMN released from the bone marrow by cigarette smoking preferentially sequestered in pulmonary microvessels and speculate that these PMN may contribute to the alveolar wall damage associated with smoke-induced lung emphysema.
我们实验室的研究表明，长期接触香烟烟雾会导致中性粒细胞增多，这与多形核白细胞（PMN）通过骨髓有丝分裂后池的平均转运时间缩短有关。本研究旨在验证以下假设：烟雾暴露从骨髓新释放的PMN优先滞留于肺微血管中。胸腺嘧啶类似物5'-溴-2'-脱氧尿苷（BrdU）用于标记兔骨髓中正在分裂的PMN；使用免疫细胞化学方法检测它们在循环中的出现情况，并使用标准形态计量技术确定它们在肺组织中的滞留情况。与假暴露对照动物（n = 4）相比，暴露于香烟烟雾11天的动物（n = 6）循环中的PMN计数没有增加，但带状细胞百分比增加（吸烟组为9.8 +/- 1.1%，对照组为5.5 +/- 0.9%；P < 0.05），循环中BrdU标记的PMN（PMNBrdU）也增加（吸烟组为10.8 +/- 0.6%，对照组为7.5 +/- 0.3%；P < 0.05）。烟雾暴露动物肺中滞留的PMN（51.7 +/- 3.4 x 10(7)/ml组织）比对照动物（25.1 +/- 1.8 x 10(7)/ml组织）更多（P < 0.05），并且这些细胞中PMNBrdU的百分比更高（吸烟组为16.9 +/- 2.3%，对照组为9.6 +/- 0.4%；P < 0.05）。在烟雾暴露组中，肺的非重力依赖区域（11.7 +/- 1.9%）的PMNBrdU百分比高于重力依赖区域（7.8 +/- 1.8%）（P < 0.05）。透射电子显微镜显示烟雾暴露组肺毛细血管内皮损伤，有粘附的PMN。我们得出结论，吸烟从骨髓释放的较年轻PMN优先滞留于肺微血管中，并推测这些PMN可能导致与烟雾诱导的肺气肿相关的肺泡壁损伤。
