title: The effect of sanguinarine on human peripheral blood neutrophil viability and functions.
abstract: Human polymorphonuclear cell (PMN) viability, morphology, adherence, chemotaxis, oxidative metabolism, degranulation and phagocytosis were evaluated following treatment with sanguinarine (SANG). SANG was noncytotoxic to PMNs at all concentrations tested (0.31-200 microM). SANG entered the PMNs rapidly without altering the membrane fluidity and localized in the nuclear matrix. SANG (1.56-6.21 microM) inhibited chemotaxis, chemokinesis and adhesion in a dose-dependent manner, with a complete inhibition at 6.2 microM concentration. Concentrations of SANG up to 1.56 microM did not affect PMN oxidative burst; however, higher concentrations were found to inhibit basal as well as PMA-induced superoxide anion generation. The effect of SANG was time- and dose-dependent, and could be reversed if the PMNs were exposed to 12.5 microM or lower concentrations of SANG for less than 5 min. Autologous serum increased the tolerance of PMNs to SANG. Exogenous Ca2+ or Mg2+ did not alter the SANG-mediated inhibition of PMN functions. Treatment of PMNs with 3.12 microM or higher concentrations of SANG also resulted in inhibition of PMN degranulation and phagocytosis. The results suggest that SANG-mediated inhibition of PMN functions, without cytolysis or resultant release of inflammatory mediators, may have clinical implications.
authors.affiliation: Department of Periodontics, University of Maryland Dental School, Baltimore.
authors.forename: S
authors.initials: S
authors.lastname: Agarwal
authors.forename: M A
authors.initials: MA
authors.lastname: Reynolds
authors.forename: S
authors.initials: S
authors.lastname: Pou
authors.forename: D E
authors.initials: DE
authors.lastname: Peterson
authors.forename: J A
authors.initials: JA
authors.lastname: Charon
authors.forename: J B
authors.initials: JB
authors.lastname: Suzuki
mesh_terms: D000470:Alkaloids / Q000494:pharmacology*; D000890:Anti-Infective Agents / Q000494:pharmacology*; D053119:Benzophenanthridines; D002448:Cell Adhesion / Q000187:drug effects; D015550:Cell Degranulation / Q000187:drug effects; D002633:Chemotaxis / Q000187:drug effects; D006801:Humans; D007546:Isoquinolines; D008560:Membrane Fluidity / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects*; D010587:Phagocytosis / Q000187:drug effects; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000470:Alkaloids; D000890:Anti-Infective Agents; D053119:Benzophenanthridines; D007546:Isoquinolines; C005705:sanguinarine; D013482:Superoxide Dismutase