Inflammatory and epithelial responses in mouse strains that differ in sensitivity to hyperoxic injury.
The pulmonary response to various toxicants including bleomycin, ozone, ionizing radiation, and hyperoxia is highly variable among mouse strains. The current study tests the hypothesis that at a similar stage of injury, regardless of strain, expression of inflammatory cytokine and epithelial marker genes would be similar, indicating a common pathway of injury progression. Three strains of mice, C57B1/6J, 129/J, and C3H/HeJ, ranging from sensitive to resistant, were exposed to > 95% O2 for varying times. Ribonuclease protection was used to quantify changes in cytokine mRNA. Despite differences in the kinetics, each strain demonstrated similar hyperoxia-induced changes in the abundance of interleukin (IL)-6, IL-1 beta, IL-3, and tumor neucrosis factor (TNF)-alpha. For each strain, death was accompanied by similar increases in cytokine mRNAs above steady-state control levels. Other inflammatory cytokines, including IL-1 alpha, IL-4, and interferon (IFN)-gamma, were unaltered in all strains at all times. In situ hybridization analysis of the epithelial markers, surfactant protein B (SPB), and clara cell secretory protein (CCSP) at the time of proinflammatory induction showed a similar pattern of expression in all strains. Increased SPB was detected in bronchiolar epithelium, while the number of type II cells expressing this message declined. Both the number of cells expressing CCSP as well as abundance per cell declined. These results suggest that although differences in acute sensitivity to hyperoxia exist between mouse strains, once initiated, acute epithelial cell injury and associated inflammatory changes follow the same pattern in all strains.
Johnston
C J
CJ
Department of Environmental Medicine, Strong Children's Research Center, University of Rochester School of Medicine and Dentistry, New York 14642, USA.
Stripp
B R
BR
Piedbeouf
B
B
Wright
T W
TW
Mango
G W
GW
Reed
C K
CK
Finkelstein
J N
JN
D000818:Animals; D016207:Cytokines / Q000096:biosynthesis*; D004848:Epithelium / Q000378:metabolism; D018496:Hyperoxia / Q000150:complications* / Q000378:metabolism*; D008171:Lung Diseases / Q000139:chemically induced* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D010100:Oxygen / Q000633:toxicity*; D014176:Protein Biosynthesis; D011510:Proteolipids / Q000096:biosynthesis*; D011663:Pulmonary Surfactants / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000378:metabolism; D012260:Ribonucleases / Q000378:metabolism; D012680:Sensitivity and Specificity; D013045:Species Specificity; D014598:Uteroglobin
D016207:Cytokines; D011510:Proteolipids; D011663:Pulmonary Surfactants; D012333:RNA, Messenger; C556390:Scgb1a1 protein, mouse; D014598:Uteroglobin; D012260:Ribonucleases; D010100:Oxygen