Ofulue A F, Ko M
Respiratory Division, Department of Medicine, The University of British Columbia, Vancouver, British Columbia, Canada V6H 3Z6.
Am J Physiol. 1999 Jul;277(1):L97-105. doi: 10.1152/ajplung.1999.277.1.L97.
The aim of this study was to ascertain the putative roles of neutrophils or macrophages in the pathogenesis of cigarette smoking-induced emphysema on the basis of effects of anti-neutrophil (anti-PMN) antibody or anti-monocyte/macrophage (anti-MoMac) antibody on the development of emphysema in cigarette smoke-exposed rats. Rats were treated with rabbit anti-PMN or anti-MoMac antibody and exposed 7 days/wk for 2 mo to cigarette smoke inhalation; rats treated with nonimmunized rabbit IgG (control antibody) and exposed to cigarette smoke or normal room air served as controls. Antibody treatments began 24 h before the start of smoke or air exposure and was continued with 1 treatment/wk. Total and differential cell counts in bronchoalveolar lavage fluid and collagenase-dissociated lung and determinations of the elastinolytic activity of lung neutrophils or macrophages in [(3)H]elastin-coated wells indicated specific suppression of neutrophil accumulation and neutrophil-related elastinolytic burden in the lungs of the anti-PMN antibody-treated smoke-exposed rats, in contrast to specific suppression of macrophage accumulation and macrophage-related elastinolytic burden in the lungs of the anti-MoMac antibody-treated smoke-exposed rats. Cigarette smoke exposure-induced lung elastin breakdown (quantitated by immunologic assay of levels of elastin-derived peptides and desmosine in lavage fluid) and emphysema in the lungs (based on morphometric analysis of alveolar mean linear intercepts and alveolar tissue density in fixed lungs) were not prevented in the lungs of anti-PMN antibody-treated smoke-exposed rats but was clearly prevented in lungs of the anti-MoMac antibody-treated smoke-exposed rats. These findings implicate macrophages rather than neutrophils as the critical pathogenic factor in cigarette smoke-induced emphysema.
本研究的目的是基于抗中性粒细胞（抗PMN）抗体或抗单核细胞/巨噬细胞（抗MoMac）抗体对暴露于香烟烟雾的大鼠肺气肿发展的影响，确定中性粒细胞或巨噬细胞在吸烟诱导的肺气肿发病机制中的假定作用。大鼠用兔抗PMN或抗MoMac抗体治疗，并每周7天、持续2个月暴露于香烟烟雾吸入；用未免疫的兔IgG（对照抗体）治疗并暴露于香烟烟雾或正常室内空气的大鼠作为对照。抗体治疗在烟雾或空气暴露开始前24小时开始，每周进行1次治疗。支气管肺泡灌洗液和胶原酶解离肺中的总细胞计数和分类细胞计数，以及在[³H]弹性蛋白包被孔中测定肺中性粒细胞或巨噬细胞的弹性蛋白酶活性，表明抗PMN抗体治疗的烟雾暴露大鼠肺中中性粒细胞积聚和中性粒细胞相关的弹性蛋白酶负荷受到特异性抑制，相比之下，抗MoMac抗体治疗的烟雾暴露大鼠肺中巨噬细胞积聚和巨噬细胞相关的弹性蛋白酶负荷受到特异性抑制。香烟烟雾暴露诱导的肺弹性蛋白分解（通过对灌洗液中弹性蛋白衍生肽和锁链素水平的免疫测定进行定量）和肺中的肺气肿（基于对固定肺中肺泡平均线性截距和肺泡组织密度的形态计量分析）在抗PMN抗体治疗的烟雾暴露大鼠肺中未得到预防，但在抗MoMac抗体治疗的烟雾暴露大鼠肺中明显得到预防。这些发现表明巨噬细胞而非中性粒细胞是香烟烟雾诱导的肺气肿的关键致病因素。
