title: Enhancing and priming of macrophages for superoxide anion production by taxol.
abstract: Taxol, an anticancer drug, has been known not only to block cell division by stabilizing microtubules but also to activate murine macrophages to express TNF-alpha, interleukin-1, and to produce nitric oxide (NO). We therefore reasoned that taxol could activate murine macrophages to generate reactive oxygen intermediates, such as superoxide anion (O2-), which are responsible for intracellular killing of pathogenic microbes. Treatment of RAW264.7 cells, murine macrophage cell line, with taxol increased phorbol ester-induced O2- production in a dose dependent manner (approximately 2 fold). In addition, taxol rapidly (< 1 hr) primed RAW264.7 cells to enhance O2- release stimulated with PMA. Taxol also enhanced stimulation of O2- production by FMLP, but not by Con A. This effect was abolished by prior treatment with both superoxide dismutase (SOD) and N-acetyl-L-cystein, a free radical scavenger. To investigate the mechanism of taxol-induced macrophage stimulation, we evaluated the ability of colchicine, a drug that inhibit tubulin polymerization, and cAMP analogues, which is known to depolymerize microtubule. Taxol-induced O2- production was inhibited by the treatment with both colchicine and DB-cAMP. Taken together, these results demonstrated that taxol provides two signals, "priming" and "enhancing", to generate superoxide anion via the stabilization of microtubules in murine RAW264.7 cells
authors.affiliation: Department of Microbiology and Immunology, Wonkwang University School of Medicine, Chonbuk, Korea.
authors.forename: H O
authors.initials: HO
authors.lastname: Pae
authors.forename: C D
authors.initials: CD
authors.lastname: Jun
authors.forename: J C
authors.initials: JC
authors.lastname: Yoo
authors.forename: H J
authors.initials: HJ
authors.lastname: Kwak
authors.forename: S J
authors.initials: SJ
authors.lastname: Lee
authors.forename: Y A
authors.initials: YA
authors.lastname: Kook
authors.forename: R K
authors.initials: RK
authors.lastname: Park
authors.forename: H T
authors.initials: HT
authors.lastname: Chung
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D003994:Bucladesine / Q000494:pharmacology; D002460:Cell Line; D003078:Colchicine / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects*; D051379:Mice; D017239:Paclitaxel / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D013481:Superoxides; D003994:Bucladesine; D013755:Tetradecanoylphorbol Acetate; D017239:Paclitaxel; D003078:Colchicine