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

在肺间质性疾病中，肺泡巨噬细胞（AM）在肺组织损伤和纤维化中起核心作用。AM的来源是血液单核细胞的募集和局部增殖。然而，AM的增殖过程尚不完全清楚。在本研究中，我们研究了特发性肺纤维化（IPF）患者AM上转铁蛋白受体（TFR）的特征，以阐明AM复制的过程。在健康受试者中，吸烟AM与不吸烟AM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。在IPF患者中，即使在非吸烟者中，也发现TFR阳性AM的比例和细胞表面的TFR数量减少，而TFR的亲和力增加。为了评估细胞活化对TFR对AM特性的影响，我们研究了LPS、PMA或< γ >-干扰素刺激AM的TFR，发现所有这些试剂都增加了TFR的亲和力，减少了细胞表面TFR的数量。由于发现积极复制pha刺激的血液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。研究了TFR对铁饱和转移蛋白的亲和力，并将其与IPF患者AM中的转铁蛋白进行了比较，在三分之二的病例中，TFR对转铁蛋白的亲和力更高，表明IPF患者TFR存在结构异常。为了评估tfr基因遗传缺陷的可能性，采用TFR-cDNA进行Northern blotting分析，检测TFR-mRNA的大小。然而，IPF与正常受试者之间没有差异。在血液单核细胞中，dot blotting分析tfr -基因的表达，单核细胞显示有少量的TFR-mRNA作为静息淋巴细胞。

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.