Blocking E-selectin Alleviates LPS-induced Acute Lung Injury In Mice

E-selectin is an important cell adhesion molecule expressed only on endothelial cells,and plays an important role in recruiting leukocytes during acute inflammatory lung injury.Here, we tested the hypothesis that blocking E-selectin could protect against the acute lunginjury (ALI). E-selectin deficient and the wide type control mice were treated with LPS toinduce ALI. Twelve hours late, the body temperature was measured with a thermal imagingcamera. The lung tissues, blood samples, and bronchoalveolar lavage fluid (BALF)samples were collected for the following measures: expression of E-selectin andmyeloperoxidase (MPO), malondialdehyde (MDA) contents, wet/dry lung weight ratio,and histological examinations. Representative, proinflammatory cytokines were measuredin the serum. LPS challenge increased gene expression of cell adhesion molecules,especially E-selectin. Compared with the wild-type control, E-selectin deficient mice hadsignificantly lower serum TNF-α level, fewer white blood cells in the BALF, and lowerMDA content and MPO expression in lung tissues.In a separate set of in vitro experiments, cimetidine (100μM) dramatically suppressedthe expression of E-selectin in LPS-treated human umbilical vein endothelial cells(HUVEC). The body temperature dropped at12h after LPS challenge in the wide-typecontrol mice, but remained relatively stable in E-selectin deficient or cimetidine-pretreatedmice. The survival rate of E-selectin deficient or cimetidine-pretreated mice wassignificantly improved compared with their controls in LPS-induced ALI. In conclusion, the present study demonstrated that blocking E-selectin could alleviate LPS-induced ALI,and the beneficial effect of cimetidine on ALI may be attributed to inhibition of E-selectin.