Endothelium-derived Toll-like receptor-4 is the key molecule in XXXX -induced neutrophil sequestration into lungs.

@entity558 @entity19 @entity358 @entity1990 @entity204
The rapid and selective accumulation of neutrophils into the lungs is thought to underlie the @entity358 that leads to sepsis-related @entity204 . In this study we investigated whether neutrophil @entity1990 is important in @entity558 -induced pulmonary neutrophil recruitment by creating chimeric @entity19 (transferring bone marrow between @entity1990 (+/+) and @entity1990 (-/-) @entity19 ). In @entity1990 (+/+) @entity19 receiving @entity1990 (-/-) bone marrow, 6 weeks after transplant @entity1990 was absent in all circulating leukocytes as well as in resident macrophages (these @entity19 were termed LeukocyteTLR4(-/-)), and these cells were completely nonresponsive to @entity558 . In @entity1990 (-/-) @entity19 receiving @entity1990 (+/+) bone marrow, endothelial cells but not leukocytes were deficient in @entity1990 (EndotheliumTLR4(-/-)). Surprisingly, systemic @entity558 (0.5 mg/kg) induced a dramatic increase in neutrophil sequestration into the lungs of LeukocyteTLR4(-/-) @entity19 over the first 4 hours. Concomitantly, numbers of circulating leukocytes decreased by 90%. By contrast, EndotheliumTLR4(-/-) @entity19 showed very little increase in neutrophil sequestration in the lungs, suggesting that endothelium rather than leukocyte @entity1990 was important. Intravital microscopy of peripheral microcirculation in the cremaster muscle revealed about 30-fold more leukocyte-endothelial cell interactions in @entity558 -treated EndotheliumTLR4(-/-) @entity19 than in @entity558 -treated LeukocyteTLR4(-/-) @entity19 . This is consistent with less sequestration of leukocytes into the lungs of EndotheliumTLR4(-/-) @entity19 . In conclusion, our data challenge the view that @entity558 directly activates neutrophils to trap in lungs and suggest a far more important role than previously appreciated for the endothelial cells.
