| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2000: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1999: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1998: ¥2,100,000 (Direct Cost: ¥2,100,000)
|
|---|
| Research Abstract |
Radiation therapy widely used for treating of thoracic malignancies often induces damage to normal lung tissue, esulting in radiation pneumonitis and pulmonary fibrosis. Pathologically, radiation pneumonitis is characterized by interstitial edema, infiltration of interstitial and alveolar inflammatory cells, increased Type II pneumocytes, fibrotic reaction by increased interstitial collagen deposition, thickening of vascular walls.
To clarify the role of thrombin in the pathogenesis of radiation-induced pneumonitis, we measured the thrombin activity and fibroblast growth-inducing activity in bronchoalveolar lavage fluid (BALF) obtained from irradiated rat lungs. Bronchoalveolar lavage fluid was collected at 1, 2, 4, 8 and 18 weeks after the irradiation. Higher fibroblast growth-inducing activity was detected in the BALF from irradiated rats at 4 and 18 weeks than from unirradiated rats. Pretreatment of BALF from irradiated rats at 4 weeks with thrombin inhibitors, antithrombin III and a
… More
rgatroban, significantly inhibited the fibroblast growth-inducing activity as well as the thrombin activity. On the other hand, these thrombin inhibitors did not inhibit fibroblast growth-inducing activity in BALF from irradiated rats at 18 weeks. Purified rat thrombin induced proliferation of fibroblasts from irradiated rats similar to those from unirradiated rats. These findings suggest that thrombin may play an important role as a fibroblast growth-inducing factor during early stages of radiation pneumonitis.
CD13/aminopeptidase N is a cell surface glycoprotein widely distributed in a variety of mammalian cells. CD13/aminopeptidase N has chemotactic activity for T lymphocytes, We examined the role of CD13/aminopeptidase N on lymphocytic alveolitis in radiation-induced lung injury in a rat model. Significantly increased aminopeptidase activity was detected in BALF obtained from irradiated rats at 4 weeks after irradiation compared with the activity in unirradiated rats. Significantly higher aminopeptidase activity was detected on alveolar macrophages (AM) from irradiated rats at 2 and 4 weeks than from unirradiated rats. Western blot analysis showed increased expression of CD13/aminopeptidase N protein in AM from irradiated rats at 4 weeks. Chemotactic activity for normal rat lymphocytes was detected in the BALF from irradiated rats at 4 weeks, and approximately sixty percent of the activity was inhibited by pretreatment of BALF with bestatin, a specific aminopeptidase inhibitor. This study suggests that CD13/aminopeptidase N may be important as a lymphocyte chemoattractant in lymphocyte-mediated alveolitis in experimental radiation-induced lung injury. Less
|
