Gender differences in pulmonary regenerative response to naphthalene-induced bronchiolar epithelial cell injury.
OBJECTIVE
Accumulating evidence suggests that gender affects the incidence and severity of several pulmonary diseases. Previous studies on mice have shown gender differences in susceptibility to naphthalene-induced lung injury, where Clara cell damage was found to occur earlier and to be more extensive in females than in males. However, very little is known about whether there are any gender differences in subsequent lung repair responses. The aim of this study was to investigate whether gender plays an important role in pulmonary regenerative response to naphthalene-induced Clara cell ablation.


METHODS
Adult male and female mice were injected with a low, medium, or high dose of naphthalene, and lung tissue regeneration was examined by immunohistochemical staining for cell proliferation marker (Ki-67) and mitosis marker (phosphohistone-3).


RESULTS
Histopathological analysis showed that naphthalene-induced Clara cell necrosis was more prominent in the lungs of female mice as compared to male mice. Cell proliferation and mitosis in both the distal bronchiolar airway epithelium and peribronchiolar interstitium of female mice was significantly greater than that of male mice after treatment with the low and medium doses. However, after treatment with high dose of naphthalene, lung regeneration was delayed in female mice, while male mice mounted a timely regenerative response.


CONCLUSIONS
These findings show that there are clear gender differences in naphthalene-induced lung injury and repair.
Oliver
J R
JR
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
Kushwah
R
R
Wu
J
J
Cutz
E
E
Yeger
H
H
Waddell
T K
TK
Hu
J
J
D055371:Acute Lung Injury / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D000367:Age Factors; D000818:Animals; D055745:Bronchioles / Q000473:pathology / Q000503:physiopathology; D002455:Cell Division / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008938:Mitosis / Q000502:physiology; D009281:Naphthalenes / Q000633:toxicity*; D009336:Necrosis; D012038:Regeneration / Q000502:physiology; D020545:Respiratory Mucosa / Q000473:pathology* / Q000502:physiology*; D012720:Severity of Illness Index; D012727:Sex Characteristics
D019394:Ki-67 Antigen; C498355:Mki67 protein, mouse; D009281:Naphthalenes; C031721:naphthalene