Suppression of endotoxin-induced inflammation by taxol.
The pathogenesis of acute lung injury includes transendothelial diapedesis of leukocytes into lung tissues and disruption of endothelial/epithelial barriers leading to protein-rich oedema. In vitro studies show that the microtubule network plays a role in the regulation of endothelial permeability as well as in neutrophil locomotion. It was hypothesised that the microtubule-stabilising agent, taxol, might attenuate inflammation and vascular leak associated with acute lung injury in vivo. The effect of intravenously delivered taxol was assessed using a model of murine lung injury induced by intratracheal lipopolysaccharide (LPS) administration. Parameters of lung injury and inflammation were assessed 18 h after treatment. Intravenously delivered taxol significantly reduced inflammatory histological changes in lung parenchyma and parameters of LPS-induced inflammation: infiltration of proteins and inflammatory cells into bronchoalveolar lavage fluid, lung myeloperoxidase activity, and extravasation of Evans blue-labelled albumin into lung tissue. Taxol alone (in the absence of LPS) had no appreciable effect on these parameters. In addition to lung proteins, intravenous taxol reduced accumulation of leukocytes in ascitic fluid in a model of LPS-induced peritonitis. Taken together, the present data demonstrate that microtubule stabilisation with taxol systemically attenuates lipopolysaccharide-induced inflammation and vascular leak.
Mirzapoiazova
T
T
Vascular Biology Center, Medical College of Georgia, Augusta, GA 30912-2500, USA.
Kolosova
I A
IA
Moreno
L
L
Sammani
S
S
Garcia
J G N
JG
Verin
A D
AD
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D019559:Capillary Leak Syndrome / Q000276:immunology / Q000473:pathology; D019446:Endotoxemia / Q000276:immunology* / Q000473:pathology; D005119:Extravasation of Diagnostic and Therapeutic Materials / Q000276:immunology / Q000473:pathology; D007958:Leukocyte Count; D008070:Lipopolysaccharides / Q000276:immunology*; D008168:Lung / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D017239:Paclitaxel / Q000494:pharmacology*; D010538:Peritonitis / Q000276:immunology / Q000473:pathology; D009195:Peroxidase / Q000378:metabolism; D011654:Pulmonary Edema / Q000276:immunology / Q000473:pathology; D012128:Respiratory Distress Syndrome / Q000276:immunology* / Q000473:pathology; D018746:Systemic Inflammatory Response Syndrome / Q000276:immunology* / Q000473:pathology; D050257:Tubulin Modulators / Q000494:pharmacology*
D008070:Lipopolysaccharides; D050257:Tubulin Modulators; D009195:Peroxidase; D017239:Paclitaxel