Thrombin promotes fibroblast proliferation during the early stages of experimental radiation pneumonitis.
Huang, L., Ogushi, F., Tani, K., Ogawa, H., Kawano, T., Endo, T., Izumi, K., Ueno, J., Nishitani, H. and Sone, S. Thrombin Promotes Fibroblast Proliferation during the Early Stages of Experimental Radiation Pneumonitis. Radiat. Res. 156, 45-52 (2001). 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 obtained from the irradiated lungs of rats at 1, 2, 4, 8 and 18 weeks after irradiation. Thrombin activity was not detected in the bronchoalveolar lavage fluid from unirradiated rats, but the bronchoalveolar lavage fluid from irradiated rats showed significantly increased thrombin activity which reached a maximum at 4 weeks after treatment. Higher fibroblast growth-inducing activity was detected in the bronchoalveolar lavage fluid from irradiated rats at 4 and 18 weeks than in fluid from unirradiated rats. Bronchoalveolar lavage fluid from irradiated rats that were pretreated with the thrombin inhibitors antithrombin III and argatroban showed significantly inhibited fibroblast growth-inducing activity and thrombin activity at 4 weeks. However, these thrombin inhibitors did not inhibit fibroblast growth-inducing activity in bronchoalveolar lavage fluid from irradiated rats at 18 weeks. Purified rat thrombin similarly induced proliferation of fibroblasts derived from irradiated and unirradiated rats. These findings suggest that thrombin may play an important role as a fibroblast growth-inducing factor during the early stages of radiation pneumonitis.
Huang
L
L
Third Department of Internal Medicine, School of Medicine, Tokushima University, 3-18-15 Kuramoto-cho, Tokushima city 770-8503, Japan.
Ogushi
F
F
Tani
K
K
Ogawa
H
H
Kawano
T
T
Endo
T
T
Izumi
K
K
Sono
N
N
Ueno
J
J
Nishitani
H
H
Sone
S
S
D000818:Animals; D000990:Antithrombin III / Q000494:pharmacology; D000991:Antithrombins / Q000494:pharmacology; D001120:Arginine / Q000031:analogs & derivatives; D001681:Biological Assay; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002455:Cell Division / Q000187:drug effects; D002469:Cell Separation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D006133:Growth Substances / Q000032:analysis / Q000494:pharmacology; D008168:Lung / Q000473:pathology / Q000528:radiation effects; D008297:Male; D010875:Pipecolic Acids / Q000494:pharmacology; D011833:Radiation Injuries, Experimental / Q000378:metabolism* / Q000473:pathology; D017564:Radiation Pneumonitis / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D013047:Specific Pathogen-Free Organisms; D013449:Sulfonamides; D013917:Thrombin / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology
D000991:Antithrombins; D006133:Growth Substances; D010875:Pipecolic Acids; D013449:Sulfonamides; D000990:Antithrombin III; D001120:Arginine; D013917:Thrombin; C031942:argatroban