TLR4 is essential in acute lung injury induced by unresuscitated hemorrhagic shock.
BACKGROUND
Acute lung injury (ALI) and acute respiratory distress syndrome in patients with hemorrhagic shock (HS) or resuscitation is associated with the expression of TLR4. However, the role of TLR4 in ALI induced by unresuscitated HS remains obscure.


METHODS
The lung pathologic change was observed by hematoxylin and eosin staining. Interleukin-1beta and tumor necrosis factor-alpha were analyzed by enzyme-linked immunosorbent assay. Polymorphonuclear leukocyte sequestration and lung leak were analyzed by pulmonary myeloperoxidase activity and Evans blue dye. The expressions of TLR4 mRNA and protein were analyzed by reverse transcription-polymerase chain reaction and Western blot, respectively. TLR4 distribution was analyzed by immunohistochemistry.


RESULTS
Lung neutrophil accumulation and microvascular permeability were significantly increased after unresuscitated HS, meanwhile, lung interleukin-1beta and tumor necrosis factor-alpha were gradually augmented. TLR4 mRNA, TLR4 distribution and TLR4 protein were also significantly increased in TLR4 wt mice, however, no above-mentioned changes appeared in TLR4 mutant mice.


CONCLUSIONS
TLR4 is strongly associated with the pathogenesis of ALI induced by unresuscitated HS, which may serve as a useful therapeutic target.
Lv
Tangfeng
T
Department of Respiratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu Province, People's Republic of China.
Shen
Xiaokun
X
Shi
Yi
Y
Song
Yong
Y
D055371:Acute Lung Injury / Q000209:etiology / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D007124:Immunoenzyme Techniques; D007375:Interleukin-1 / Q000378:metabolism; D008070:Lipopolysaccharides; D008233:Lymphotoxin-alpha / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011897:Random Allocation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012771:Shock, Hemorrhagic / Q000150:complications / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
D007375:Interleukin-1; D008070:Lipopolysaccharides; D008233:Lymphotoxin-alpha; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4