Mancini N M, Béné M C, Gérard H, Chabot F, Faure G, Polu J M, Lesur O
Service des Maladies Respiratoires et Réanimation Respiratoire, CHRU Nancy-Brabois, Vandoeuvre Les Nancy, France.
Lung. 1993;171(5):277-91. doi: 10.1007/BF03215871.
We investigated the early effects of cigarette smoking in healthy subjects by means of lung lavage, looking at markers of alveolar permeability, the alveolar cell profile, the immunophenotyping of macrophages and lymphocytes, and the level and profile of surfactant phospholipids. Bronchoalveolar lavages (BAL) were performed in 33 healthy subjects [20 nonsmokers (nS), 13 moderate and short-time smokers (S)]. In the acellular supernatants we measured the markers of alveolar permeability (i.e., total proteins, albumin, albumin/urea), the alveolar epithelial lining fluid (AELF), the surfactant amounts and profile, and explored the blood lymphocytes by in vitro exposure. The cell pellet established the alveolar formula and a membrane mapping of macrophages (LFA-1 and HLA-DRII expression) and lymphocytes (CD4, CD8, LFA-1, HLA-DRII expression). We found no significant increase of alveolar permeability in our smokers, but an increased alveolar cellularity (more than 3-fold vs nS, P < 0.05) evenly distributed between sub-populations except for an enhanced number of eosinophils in smokers (P < 0.05 vs nS). Smokers' alveolar macrophages had an overloaded cytoplasm, a decreased percentage of antigen-handling cell expression (HLA DRII: P < 0.05 vs nS) and a low percentage of cell to cell adhesion molecule expression (LFA-1: P < 0.05 vs nS). Smoking history and LFA-1 expression on alveolar macrophages were interrelated. Smokers' alveolar lymphocyte subsets were more often T suppressor cells (CD8+) and had an increased percentage of antigen-presenting cell expression (HLA DRII: P < 0.05 vs nS). Smokers' BAL fluid did not show the inhibitory control of phytohemagglutinin-induced lymphocyte proliferation present in nonsmokers' fluids. Surfactant phospholipid amounts were similar, but phosphatidylethanolamine was raised and the ratio of phosphatidylcholine to sphingomyelin decreased in smokers (P < 0.05 vs nS). We observed specific cellular and biochemical alterations in the lung lavage of short-time smokers. Alveolar macrophage and lymphocyte expression of LFA-1 and HLA-DR II molecules was altered. Smokers' alveolar fluids lost the physiologic regulatory control of T mitogen-induced lymphocyte proliferation. Membrane phospholipids released by cellular damage increased early in tobacco-exposed lung fluids. This profile of alterations may be an early and sensitive marker of smoking-induced lung damage.
我们通过肺灌洗研究了吸烟对健康受试者的早期影响，观察了肺泡通透性标志物、肺泡细胞谱、巨噬细胞和淋巴细胞的免疫表型，以及表面活性物质磷脂的水平和谱。对33名健康受试者[20名不吸烟者（nS），13名中度短期吸烟者（S）]进行了支气管肺泡灌洗（BAL）。在无细胞上清液中，我们测量了肺泡通透性标志物（即总蛋白、白蛋白、白蛋白/尿素）、肺泡上皮衬液（AELF）、表面活性物质的量和谱，并通过体外暴露研究了血液淋巴细胞。细胞沉淀确定了肺泡公式以及巨噬细胞（LFA-1和HLA-DRII表达）和淋巴细胞（CD4、CD8、LFA-1、HLA-DRII表达）的膜图谱。我们发现吸烟者的肺泡通透性没有显著增加，但肺泡细胞增多（与nS相比增加了3倍以上，P<0.05），除吸烟者中嗜酸性粒细胞数量增加外（与nS相比P<0.05），各亚群之间分布均匀。吸烟者的肺泡巨噬细胞细胞质过载，抗原处理细胞表达百分比降低（HLA DRII：与nS相比P<0.05），细胞间粘附分子表达百分比降低（LFA-1：与nS相比P<0.05）。吸烟史与肺泡巨噬细胞上的LFA-1表达相关。吸烟者的肺泡淋巴细胞亚群更常为T抑制细胞（CD8+），抗原呈递细胞表达百分比增加（HLA DRII：与nS相比P<0.05）。吸烟者的BAL液未显示出不吸烟者的BAL液中存在的对植物血凝素诱导的淋巴细胞增殖的抑制控制。表面活性物质磷脂的量相似，但吸烟者中磷脂酰乙醇胺升高，磷脂酰胆碱与鞘磷脂的比例降低（与nS相比P<0.05）。我们在短期吸烟者的肺灌洗中观察到了特定的细胞和生化改变。肺泡巨噬细胞和淋巴细胞LFA-1和HLA-DR II分子的表达发生了改变。吸烟者的肺泡液失去了对T有丝分裂原诱导的淋巴细胞增殖的生理调节控制。细胞损伤释放的膜磷脂在烟草暴露的肺液中早期增加。这种改变谱可能是吸烟诱导的肺损伤的早期敏感标志物。
