| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1987: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1986: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Research Abstract |
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.
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