THE EFFECT OF SANGUINARINE ON HUMAN PERIPHERAL-BLOOD NEUTROPHIL VIABILITY AND FUNCTIONS

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 mu-M). SANG entered the PMNs rapidly without altering the membrane fluidity and localized in the nuclear matrix. SANG (1.56-6.21 mu-M) inhibited chemotaxis, chemokinesis and adhesion in a dose-dependent manner, with a complete inhibition at 6.2 mu-M concentration. Concentrations of SANG up to 1.56 mu-M 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 mu-M 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 mu-M 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.