Strain dependent differences in a histological study of CD44 and collagen fibers with an expression analysis of inflammatory response-related genes in irradiated murine lung.
Using a mouse model, we investigated the mechanisms of heterogeneity in response to ionizing radiation in this research. C57BL/6J and C3H/HeMs mice were irradiated with gamma rays at 10 and 20 Gy. The animals were sacrificed at times corresponding to the latent period, the pneumonic phase, and the start of the fibrotic phase for histological investigation. Small areas of fibrosis initially appeared in C57BL/6J mice at 4 weeks postirradiation with 20 Gy, whereas small inflammatory lesions appeared at 4 and 8 weeks after 20 and 10 Gy, respectively. The alveoli septa were thickened by an infiltration of inflammatory cells, and alveoli were obliterated in lungs from C57BL/6J mice after 20 Gy irradiation. At 24 hours and from 2 to 4 weeks postirradiation, fourfold more CD44 positive cells had accumulated in the lungs of C3H/HeMs than in C57BL/6J mice. Hyaluronan accumulated 12 hours after irradiation, and the rapid resolution was achieved within 2 weeks in the lungs in both strains of mice. C57BL/6J mice lungs accumulated dense collagen at 8 weeks. Quantitative RT-PCR assay was performed for several genes selected by cDNA microarray analysis. The expression of several genes, such as Cap1, Il18, Mmp12, Per3, Ltf, Ifi202a, and Rad51ap1 showed strain-dependent variances. In conclusion, a histological investigation suggested that C3H/HeMs mice were able to induce a more rapid clearance of matrix after irradiation than C57BL/6J mice. The expression analysis showed that the several genes are potentially involved in interstrain differences in inflammatory response causing radiation-induced lung fibrosis.
Iwakawa
Mayumi
M
RadGenomics Project, Frontier Research Center, National Institute of Radiological Sciences, Chiba-shi, Japan. mayumii@nirs.go.jp
Noda
Shuhei
S
Ohta
Toshie
T
Oohira
Chisa
C
Tanaka
Hiroko
H
Tsuji
Atsushi
A
Ishikawa
Atsuko
A
Imai
Takashi
T
D000818:Animals; D003094:Collagen / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D018960:Hyaluronan Receptors / Q000378:metabolism*; D007150:Immunohistochemistry; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D017564:Radiation Pneumonitis / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D011836:Radiation Tolerance; D013045:Species Specificity
D018960:Hyaluronan Receptors; D003094:Collagen