Increased binding and chemotactic capacities of PDGF-BB on fibroblasts in radiation pneumonitis.
Although pulmonary fibrosis is a frequent and serious consequence of radiotherapy for thoracic malignant diseases such as lung cancer, the pathogenesis of this radiation-induced lung disorder remains unclear. To clarify the mechanisms underlying radiation pneumonitis and pulmonary fibrosis, we investigated the expression of platelet-derived growth factor receptor (PDGFR) on fibroblasts obtained from irradiated rat lungs and on control fibroblasts. Whole lungs of male Wistar rats were irradiated with a single dose of 15 Gy, and lung fibroblasts were isolated at 4 weeks after the irradiation. The chemotactic response of irradiated lung fibroblasts to PDGF-BB was significantly higher than that of control lung fibroblasts, whereas there was no significant difference between irradiated lung fibroblasts and control lung fibroblasts in the response to PDGF-AA. Receptor binding assay showed more specific binding sites for PDGF-BB on irradiated lung fibroblasts than on control lung fibroblasts, and the displacement of (125)I-labeled PDGF binding to fibroblasts by unlabeled PDGF showed that (125)I-labeled PDGF-BB was displaced by PDGF-BB but not by PDGF-AA. These results suggest that the increased binding sites for PDGF-BB on irradiated lung fibroblasts correspond mainly to PDGFRB. Scatchard analysis of the saturation data demonstrated an approximately twofold increase both in the number of PDGF-BB binding sites and in the binding affinity in irradiated lung fibroblasts compared to that in control lung fibroblasts. Those results suggest that the increased chemotactic response of irradiated lung fibroblasts to PDGF-BB is related to the overexpression of PDGFRB, which may have an important role in the pathogenesis of radiation-induced pneumonitis and pulmonary fibrosis.
Tada
Hiroya
H
Department of Internal Medicine and Molecular Therapeutics, Course of Medical Oncology, Tokushima University, Tokushima, Japan.
Ogushi
Fumitaka
F
Tani
Kenji
K
Nishioka
Yasuhiko
Y
Miyata
Jun-ya
JY
Sato
Keiko
K
Asano
Toru
T
Sone
Saburo
S
D000818:Animals; D000077214:Becaplermin; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002633:Chemotaxis; D005347:Fibroblasts / Q000737:chemistry; D008168:Lung / Q000737:chemistry*; D008297:Male; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D020574:Proto-Oncogene Proteins c-sis; D011658:Pulmonary Fibrosis / Q000209:etiology; D017564:Radiation Pneumonitis / Q000209:etiology / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017479:Receptors, Platelet-Derived Growth Factor / Q000032:analysis*
D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin; D017479:Receptors, Platelet-Derived Growth Factor