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3 SUPPRESSION OF LIPOPOLYSACCHARIDE-INDUCED ACUTE LUNG INJURY BY TAXOL.
  1. T. Mirzapoiazova,
  2. L. Moreno,
  3. S. Sammani,
  4. I. Kolosova,
  5. J. G. Garcia,
  6. A. D. Verin
  1. The University of Chicago, Chicago, IL

Abstract

Our prior study demonstrated that similar to actin cytoskeleton, mictotubule (MT) network is a key participant in the regulation of endothelial (EC) permeability. Disassembly of MT by pharmacological inhibitors nocodazole and vinblastine results in rearrangement of actin cytoskeleton, stress fiber formation, EC contraction, and increased permeability. MT-stabilizing agent, Taxol, prevented EC barrier dysfunction induced by MT inhibitors and significantly attenuated permeability induced by proinflammatory agonists such as thrombin in cell culture model. We hypothesized that Taxol may prevent inflammation and vascular leak associated with lung injury. The effect of Taxol was assessed employing a model of murine lung injury induced by intratracheal LPS administration (2.5 mg/kg). Our data demonstrate that intravenous Taxol (8.5 mg/kg) injected simultaneously with LPS administration dramatically reduced inflammatory histological changes in lung parenchyma, decreased infiltration of proteins (40%, p < .001) and inflammatory cells in bronchoalveolar lavage (BAL) (51%, p < .01) and extravasation of Evans blue albumin dye into lung tissue. Taxol also significantly reduced LPS-induced release of inflammatory cytokines (tumor necrosis factor α and interleukin-6) into BAL (30% for both, p < .05). At the same time Taxol alone had no appreciable effect on the parameters described above. These data suggested that MT destabilization may be involved in LPS-induced lung injury in vivo.

HL 58064; HL 60637.

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