Finkelstein R, Fraser R S, Ghezzo H, Cosio M G
Respiratory Division, Royal Victoria Hospital, Montreal, Quebec, Canada.
Am J Respir Crit Care Med. 1995 Nov;152(5 Pt 1):1666-72. doi: 10.1164/ajrccm.152.5.7582312.
The prevalent theory in the pathogenesis of emphysema proposes that increased numbers of activated neutrophils and/or alveolar macrophages produce large amounts of proteases, an activity that cannot be regulated by alpha 1-antiproteases, resulting in lung destruction. However, the cells in the lung parenchyma of smokers have not been properly identified. We characterized and quantitated the inflammatory cell load in the lungs of smokers and correlated these findings with the degree of lung destruction. Twenty-one patients, six nonsmokers and 15 smokers, undergoing lung resection were studied. Lungs or lobes were fixed and stained for light microscopy and neutrophil identification and immunohistochemically stained for identification of lymphocytes and macrophages. By point counting, we determined the extent of emphysema by the volume density of the lung parenchyma (Vvalv), and the different cell numbers per cubic millimeter in all lungs. In nonsmokers Vvalv was greater than in smokers. The number of neutrophils/mm3 of lung correlated directly with the Vvalv, (r = 0.71, p < 0.01), whereas the number of alveolar macrophages (r = -0.70) and T-lymphocytes (r = -0.78) correlated negatively with the Vvalv. The number of T-lymphocytes correlated negatively with the number of neutrophils (r = -0.58) and positively with the numbers of alveolar macrophages (r = 0.77). Our data suggest that as long as the inflammatory reaction is predominantly of neutrophils there is no destruction of the lung. However, the extent of lung destruction becomes evident, and its extent is directly related to the number of alveolar macrophages and T-lymphocytes/mm3. We conclude that the T-lymphocyte might be importantly implicated in the pathogenesis of emphysema in smokers.
肺气肿发病机制的主流理论认为，活化的中性粒细胞和/或肺泡巨噬细胞数量增加会产生大量蛋白酶，而α1抗蛋白酶无法调节这种活性，从而导致肺组织破坏。然而，吸烟者肺实质中的细胞尚未得到准确鉴定。我们对吸烟者肺部的炎症细胞负荷进行了表征和定量，并将这些结果与肺组织破坏程度相关联。研究对象为21例接受肺切除术的患者，其中包括6名非吸烟者和15名吸烟者。将肺组织或肺叶固定后进行染色，用于光学显微镜检查和中性粒细胞鉴定，并进行免疫组织化学染色以鉴定淋巴细胞和巨噬细胞。通过点计数法，我们根据肺实质的体积密度（Vvalv）确定肺气肿的程度，并计算所有肺组织中每立方毫米不同细胞的数量。非吸烟者的Vvalv大于吸烟者。肺组织中每立方毫米中性粒细胞的数量与Vvalv直接相关（r = 0.71，p < 0.01），而肺泡巨噬细胞数量（r = -0.70）和T淋巴细胞数量（r = -0.78）与Vvalv呈负相关。T淋巴细胞数量与中性粒细胞数量呈负相关（r = -0.58），与肺泡巨噬细胞数量呈正相关（r = 0.77）。我们的数据表明，只要炎症反应主要由中性粒细胞主导，肺组织就不会受到破坏。然而，肺组织破坏的程度会变得明显，且其程度与每立方毫米肺泡巨噬细胞和T淋巴细胞的数量直接相关。我们得出结论，T淋巴细胞可能在吸烟者肺气肿的发病机制中起重要作用。
