The Study of Molecular Biological Aspects of the Mechanisms of Alveolar Macrophage Proliferation in the Interstitial Pneumonia

肺泡巨噬细胞（alveolar macrophages，AM）是间质性肺疾病中肺组织损伤和纤维化的重要因素，其来源是血单核细胞的募集和局部增殖，但AM增殖的过程尚不清楚，目前的研究表明，AM的增殖机制是通过细胞因子介导的细胞因子介导的。目的：研究特发性肺纤维化（IPF）患者AM转铁蛋白受体（TFR）的特点。在健康人中，吸烟者与非吸烟者相比，TFR阳性AM的比例和AM上TFR的数量减少，TFR的亲和力增加。为探讨细胞活化对转铁蛋白受体（TFR）对AM的影响，我们研究了LPS、PMA和α-干扰素对TFR的影响<gamma>由于活跃复制的PHA刺激的血淋巴细胞和红白血病细胞系K562具有高亲和力的TFR，IPF患者的AM似乎被激活，其复制可能增强。对IPF患者AM中TFR与脱铁转铁蛋白的亲和力进行了比较，发现其中2例TFR与脱铁转铁蛋白的亲和力较高，提示IPF患者存在TFR结构异常。用北方印迹法检测IPF患者外周血单核细胞中TFR-mRNA的表达，结果表明，IPF患者外周血单核细胞中TFR-mRNA的表达量与正常对照组相比无显著性差异，而外周血单核细胞中TFR-mRNA的表达量与正常对照组相比无显著性差异。

In the interstitial lung diseases ,alveolar macrophages(AM) are known to play the central role in lung tissue damage and fibrosis.The sources of AM are the recrutement of blood monocytes and local proliferation.However,the process of AM proliferation is not yet fully understood.In the present study,we studied the characteristics of the transferrin recepters(TFR) on the AM of the patients with idiophathic pulmonary fibrosis(IPF) in order to clarify the process of AM replication.In the healthy subjects,the proportion of TFR-positive AM and the numbers of TFR on AM are found to decrease and the affinity of TFR to increase in the smoker in comparison with non-smoker.In the patients with IPF,even in the non-smoker,the proportion of TFR-positive AM and the number of TFR on the cell surface are found to decrease and the affinitity of TFR to increase.To evaluate the effect of cell activation on the property of TFR on AM,we studied the TFR of LPS,PMA, or <gamma>-interferon stimulated AM and all these reagents are found to increase the affinity of TFR and to decrease the number of cell surface TFR.Since actively replicating PHA-stimulated blood lymphocytes and erythroleukemic cell line K562 are found to have the high affinity TFR,the AM of the patients with IPF appear to be activated and their replication may be enhanced.The affinity of TFR to iron-saturated transfeffin were studied and compared to apotransferrin in AM of the patients with IPF and in two of three cases,TFR showed higher a ffinity to apotransferrin suggesting the presence of structual anormaly of TFR in the patients with IPF.To evaluate the possibility of hereditary defect of TFR-gene,the size of TFR-mRNA were evaluated by Northern blotting analysis using TFR-cDNA.However,no difference was found between IPF and normal subjects.In the blood monocytes,expression of TFR-gene was evaluated by dot blotting analysis and the monocytes were shown to have a small amount of TFR-mRNA as the resting lymphocytes.