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Rapid induction of neutrophil apoptosis by sulfasalazine: implications of reactive oxygen species in the apoptotic process
Author(s) -
Akahoshi Tohru,
Namai Rie,
Sekiyama Naho,
Tanaka Sumiaki,
Hosaka Shigeru,
Kondo Hirobumi
Publication year - 1997
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.62.6.817
Subject(s) - apoptosis , neutrophil extracellular traps , propidium iodide , reactive oxygen species , biology , sulfasalazine , dna fragmentation , kinase , immunology , cancer research , rheumatoid arthritis , inflammation , programmed cell death , microbiology and biotechnology , medicine , biochemistry , ulcerative colitis , disease
Accumulating evidence indicates that neutrophils are crucially involved in the pathogenesis of inflammatory bowel diseases and rheumatoid arthritis. We therefore investigated the effect of sulfasalazine (SSZ), which is widely used in the treatment of these diseases, on neutrophil apoptosis in vitro. The apoptosis of neutrophils was determined by morphology, a DNA histogram of propidium iodide‐stained nuclei, and DNA fragmentation. SSZ rapidly accelerated the rate of spontaneous neutrophil apoptosis within clinically relevant concentrations. This effect is unique to neutrophils because other types of leukocytes and a number of leukocyte cell lines are resistant to SSZ. Neutrophil apoptosis caused by SSZ was abrogated by a tyrosine kinase inhibitor, a protein kinase A inhibitor, and antioxidants. The subsequent results provided pharmacological evidence that the phosphorylation of tyrosine kinase and protein kinase A and generation of reactive oxygen species are involved in SSZ‐mediated neutrophil apoptosis. These data suggest that SSZ‐induced neutrophil apoptosis may account, in part, for the clinical benefits of SSZ on inflammatory bowel diseases and rheumatoid arthritis. J. Leukoc. Biol . 62: 817–826; 1997.