[Role of adhesion molecules in an animal model of endotoxin-induced acute lung injury].
We studied the role of adhesion molecules in acute lung injury caused by lipopolysaccharide (LPS). Forty-eight female guinea pigs were divided into three groups: saline (n = 12); B464, an LPS antagonist, (0.2 mg/kg i.v.) (n = 12); LPS (0.02 mg/kg i.v.) (n = 12); and LPS + B464 (n = 12). The numbers of polymorphonuclear cells (PMN) in blood sampled over 4 hours were counted. Accumulation of PMNs in the lungs was determined by counting the number of PMNs in lung-tissue samples fixed for light-microscopic examination. The lung wet-to-dry weight ratio and the 125I-albumin tissue-to-plasma ratio were used to assess lung injury. Human umbilical-vein endothelial cells were treated with B464 and then stimulated with either LPS or tumor necrosis factor. Expression of ICAM-1 and ELAM-1 was estimated by enzyme-linked immunosorbent assay. After LPS injection, light microscopy revealed decreases in peripheral PMN counts, and accumulation of PMNs in the lungs. Increases in the two indices of lung injury were also observed. These changes were attenuated by prior treatment with B464. The LPS-induced increases in ICAM-1 and ELAM-1 expression were dose-dependently suppressed by B464. These results suggest that pulmonary accumulation of activated PMNs plays an important role in LPS-induced lung injury.
Ishizaka
A
A
Department of Medicine, School of Medicine, Keio University.
Soejima
K
K
Tasaka
S
S
Kanazawa
M
M
D000208:Acute Disease; D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D019040:E-Selectin / Q000378:metabolism / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism / Q000502:physiology*; D008050:Lipid A / Q000031:analogs & derivatives; D008070:Lipopolysaccharides; D008171:Lung Diseases / Q000139:chemically induced* / Q000473:pathology
C088580:B 464; D019040:E-Selectin; D008050:Lipid A; D008070:Lipopolysaccharides; D018799:Intercellular Adhesion Molecule-1