Effects of dexamethasone on the ultrastructure of alveolar type II cells in young rats with lipopolysaccharide-induced acute lung injury.
OBJECTIVE
Alveolar type II (AT II) cells play a crucial role in the maintenance of pulmonary surfactant homeostasis and pulmonary immunity. The effects of dexamethasone (Dex) on the ultrastructure of AT II cells after acute lung injury remain unknown. This study focused on the ultrastructural changes caused by acute lung injury and on the effects of Dex administration on these ultrastructural changes in young rats.


METHODS
Seventy-two 21-day-old Sprague-Dawley rats were randomly divided into control, acute lung injury and Dex-treated groups. Rats in the lung injury group were intraperitoneally injected with 4 mg/kg lipopolysaccharide (LPS) in order to induce acute lung injury, while the control rats were injected with the same amount of normal saline (NS). The Dex-treated group was injected first with LPS followed 1 hr later by Dex (5 mg/kg) injection. Eight rats in each group were sacrificed 24, 48 and 72 hrs after LPS or NS injection. Lung samples were obtained from the lower parts of left lungs and fixed with 2.5% glutaraldehyde for transmission electron microscope examination.


RESULTS
Microvilli of AT II cells disappeared and the number of lamellar bodies (LBs) increased in the lung injury group 24 hrs after LPS injection. The ring-like arrangement of LBs around nuclei was present until 48 hrs after LPS injection. By 48 hrs after LPS injection, giant LBs with vacuole-like abnormalities appeared. The shape of nuclei became irregular and the border of the nuclei became blurred. By 72 hrs after LPS injection, the number of LBs was obviously reduced; nucleoli disappeared; and karyolysis occurred in some of the nuclei. In contrast, in the Dex-treated group, LBs crowded on one side of AT II cells and exocytosis appeared on the same side by 24 hrs after LPS injection. By 48 hrs, the number of LBs was reduced. The number of mitochondria increased, and some of them became swollen and enlarged. However, by 72 hrs, the number of LBs increased and the ring-like arrangement of LBs around the nucleus again appeared.


CONCLUSIONS
Ultrastructural changes of AT II cells following lung injury induced by LPS were time-dependent in young rats. Dex may ameliorate AT II cell injury and promote functional restoration of AT II cells in LPS-induced acute lung injury.
Shu
Lin-Hua
LH
Department of Pediatrics, Shenjing Hospital, China Medical University, Shenyang, China. shulinhua@126.com
Wei
Ke-Lun
KL
Xue
Xin-Dong
XD
Han
Xiao-Hua
XH
Shang
Yun-Xiao
YX
Cai
Xu-Xu
XX
Liu
Chun-Feng
CF
Li
Jiu-Jun
JJ
Wang
Li-Jie
LJ
D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology / Q000627:therapeutic use*; D008070:Lipopolysaccharides / Q000633:toxicity*; D011650:Pulmonary Alveoli / Q000187:drug effects* / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D012128:Respiratory Distress Syndrome / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology
D008070:Lipopolysaccharides; D003907:Dexamethasone