TY - JOUR
T1 - Hydroxylation of salicylate by activated neutrophils
AU - Bruce Davis, W.
AU - Selma Mohammed, B.
AU - Mays, Dennis C.
AU - She, Zhi Wu
AU - Mohammed, Jeannette R.
AU - Husney, Rose M.
AU - Sagone, Arthur L.
N1 - Funding Information:
Acknowledgements--This work was supported by an American Lung Association Career Investigator Award and by a University Research Challenge Award. The authors wish to thank Dr Nicholas Gerber for his scientific input and for the use of his laboratory for HPLC, and Lew J. Pawluk for his technical assistance. We also wish to thank Ruth Thinguldstad who helped in the preparation of the manuscript.
PY - 1989/11/15
Y1 - 1989/11/15
N2 - Salicylates are metabolized in vivo to hydroxylated compounds, including 2,3-dihydroxy-benzoic acid and 2,5-dihydroxybenzoic acid (gentisic acid). The present study hypothesized that activated neutrophils represent one pathway for salicylate hydroxylation. Human neutrophils were incubated in medium containing 10 mM salicylate and stimulated with phorbol myristate acetate (PMA) for 1 hr. The cell-free supernatant fractions were analyzed by HPLC. Neutrophils (1 × 106 cells) produced 55 ± 11 ng of gentisic acid. Neutrophils also produced smaller quantities of 2,3-dihydroxybenzoic acid. Antioxidant inhibitor experiments indicated that superoxide dismutase (SOD), heme protein inhibitors, and glutathione blocked gentisic acid formation, whereas catalase, mannitol, and deferoxamine failed to inhibit. Experiments with the reagent hypochlorous acid (HOCl) and the model myeloperoxidase (MPO) enzyme system did not support a role for the MPO pathway in gentisic acid formation. These findings demonstrate that activated neutrophils can hydroxylate salicylate by an unknown pathway. This pathway may contribute to the increased recovery of hydroxylated salicylates in patients with inflammatory disorders.
AB - Salicylates are metabolized in vivo to hydroxylated compounds, including 2,3-dihydroxy-benzoic acid and 2,5-dihydroxybenzoic acid (gentisic acid). The present study hypothesized that activated neutrophils represent one pathway for salicylate hydroxylation. Human neutrophils were incubated in medium containing 10 mM salicylate and stimulated with phorbol myristate acetate (PMA) for 1 hr. The cell-free supernatant fractions were analyzed by HPLC. Neutrophils (1 × 106 cells) produced 55 ± 11 ng of gentisic acid. Neutrophils also produced smaller quantities of 2,3-dihydroxybenzoic acid. Antioxidant inhibitor experiments indicated that superoxide dismutase (SOD), heme protein inhibitors, and glutathione blocked gentisic acid formation, whereas catalase, mannitol, and deferoxamine failed to inhibit. Experiments with the reagent hypochlorous acid (HOCl) and the model myeloperoxidase (MPO) enzyme system did not support a role for the MPO pathway in gentisic acid formation. These findings demonstrate that activated neutrophils can hydroxylate salicylate by an unknown pathway. This pathway may contribute to the increased recovery of hydroxylated salicylates in patients with inflammatory disorders.
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U2 - 10.1016/0006-2952(89)90681-3
DO - 10.1016/0006-2952(89)90681-3
M3 - Article
C2 - 2557038
AN - SCOPUS:0024377241
SN - 0006-2952
VL - 38
SP - 4013
EP - 4019
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
IS - 22
ER -