Effects of sulphasalazine and its metabolites on neutrophil chemotaxis, superoxide production, degranulation and translocation of cytochrome b-245.
This study describes effects of sulphasalazine, 5-amino-salicylic acid (5-ASA) and sulphapyridine on polymorphonuclear neutrophils. Chemotaxis by polymorphonuclear neutrophils incubated with 5-ASA was reduced in a concentration dependent fashion (10(-5)-10(-4) M). Degranulation and release of lysozyme and beta-glucuronidase by activated polymorphonuclear neutrophils was inhibited by sulphasalazine but inhibited by sulphasalazine (IC50: 2 x 10(-4) M) and to a lesser extent by 5-ASA (IC50: 10(-3) M). Using a cell-free system sulphasalazine was found to be a strong scavenger and 5-ASA and sulphapyridine had only weak effects. Superoxide anion production requires translocation of a cytochrome b-245 and this translocation was reduced by sulphasalazine (P less than 0.01) but not by 5-ASA or sulphapyridine. In conclusion, the intact sulphasalazine molecule has an action of its own and marked differences exist between the action of sulphasalazine and 5-ASA, which may be important for the clinical activity.
Wandall
J H
JH
Blood Transfusion Service, Massachusetts General Hospital, Boston.
D015550:Cell Degranulation / Q000187:drug effects*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D003573:Cytochrome b Group / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D008566:Membranes / Q000378:metabolism; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D013427:Sulfapyridine / Q000494:pharmacology; D012460:Sulfasalazine / Q000378:metabolism / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism*; D014178:Translocation, Genetic
D003573:Cytochrome b Group; C035130:cytochrome b245; D013481:Superoxides; D012460:Sulfasalazine; D009240:N-Formylmethionine Leucyl-Phenylalanine; D013427:Sulfapyridine