TY - JOUR
T1 - Effect of 5-aminosalicylic acid and analogous substances on superoxide generation and intracellular free calcium in human neutrophilic granulocytes
AU - Nielsen, O H
AU - Bouchelouche, P N
AU - Berild, D
AU - Ahnfelt-Rønne, I
PY - 1993/6
Y1 - 1993/6
N2 - Activated polymorphonuclear leukocytes (PMNs), which are found in the inflammatory lesions of chronic inflammatory bowel disease, produce tissue-destructive oxygen-derived free radicals. The influence of 5-aminosalicylic acid (5-ASA), its acetylated metabolite (Ac-5-ASA), sulfasalazine (SAZ), and olsalazine (OLZ) (5-ASA dimer linked by an azo group) in pharmacologically relevant concentrations (0.1-10 mM) were tested on PMN superoxide production with either the receptor-specific agent formyl-methionyl-leucyl-phenylalanine (fMLP) or the protein kinase C activator phorbol myristate acetate (PMA). Inhibition of receptor-specific superoxide production occurred at 0.07, 0.32, and 0.63 mM (IC50 values) for 5-ASA, SAZ, and OLZ, respectively. No inhibitory effects of SAZ and OLZ were observed when PMA was applied as stimulus for PMN superoxide production. The results indicate that the signal to which PMNs respond by generating superoxide is primarily due to calcium release from intracellular stores. They further suggest that SAZ and OLZ may affect the oxygen-derived free radical production in human PMNs by unspecific cytotoxicity or by interference with the nicotinamide adenine dinucleotide phosphate, reduced (NADPH) oxidase system, whereas 5-ASA itself is a free radical scavenger.
AB - Activated polymorphonuclear leukocytes (PMNs), which are found in the inflammatory lesions of chronic inflammatory bowel disease, produce tissue-destructive oxygen-derived free radicals. The influence of 5-aminosalicylic acid (5-ASA), its acetylated metabolite (Ac-5-ASA), sulfasalazine (SAZ), and olsalazine (OLZ) (5-ASA dimer linked by an azo group) in pharmacologically relevant concentrations (0.1-10 mM) were tested on PMN superoxide production with either the receptor-specific agent formyl-methionyl-leucyl-phenylalanine (fMLP) or the protein kinase C activator phorbol myristate acetate (PMA). Inhibition of receptor-specific superoxide production occurred at 0.07, 0.32, and 0.63 mM (IC50 values) for 5-ASA, SAZ, and OLZ, respectively. No inhibitory effects of SAZ and OLZ were observed when PMA was applied as stimulus for PMN superoxide production. The results indicate that the signal to which PMNs respond by generating superoxide is primarily due to calcium release from intracellular stores. They further suggest that SAZ and OLZ may affect the oxygen-derived free radical production in human PMNs by unspecific cytotoxicity or by interference with the nicotinamide adenine dinucleotide phosphate, reduced (NADPH) oxidase system, whereas 5-ASA itself is a free radical scavenger.
KW - Aminosalicylic Acids/pharmacology
KW - Calcium/metabolism
KW - Free Radical Scavengers
KW - Free Radicals
KW - Humans
KW - In Vitro Techniques
KW - Mesalamine
KW - N-Formylmethionine Leucyl-Phenylalanine/pharmacology
KW - Neutrophils/drug effects
KW - Sulfapyridine/pharmacology
KW - Sulfasalazine/pharmacology
KW - Superoxides/metabolism
KW - Tetradecanoylphorbol Acetate/pharmacology
M3 - Journal article
C2 - 8100641
SN - 0085-5928
VL - 28
SP - 527
EP - 532
JO - Scandinavian Journal of Gastroenterology. Supplement
JF - Scandinavian Journal of Gastroenterology. Supplement
IS - 6
ER -
