Serine Protease Inhibitors Inhibit Superoxide Release and Adherence in Human Neutrophils Stimulated by Granulocyte-Macrophage Colony-Stimulating Factor and Tumor Necrosis Factor-α

Abstract

Stimulation of human neutrophils with granulocyte-macrophage colony-stimulating factor (GM-CSF) or tumor necrosis factor- (TNF) results in increased superoxide (O2 -) release and adherence. O2 - release and adherence are dependent on activation of extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK). Possible participation of serine proteases in GM-CSF- or TNF-induced activation of human neutrophils was explored with various serine protease inhibitors, including phenylmethylsulfonyl fluoride, L-1-tosylamido-2-phenylethyl-chloromethyl ketone and N-α-ptosyl-L-lysine-chloromethyl ketone. GM-CSF- or TNF-induced O2 - release and adherence were inhibited in parallel by pretreatment of neutrophils with these inhibitors. On the other hand, GM-CSF- or TNF-induced phosphorylation of ERK and p38 MAPK was unaffected by these inhibitors at the concentrations effective for the inhibition of O2 - release and adherence. These findings suggest that serine proteases are involved in GM-CSF- and TNF-induced O2 - release and adherence in human neutrophils and that serine proteases function downstream or independently of the activation of ERK and p38 MAPK.

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Correspondence to Yue-Min Zhou or Haruo Kutsuna or Kenichi Suzuki or Fumihiko Hato or Seiichi Kitagawa.

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Zhou, Y., Kutsuna, H., Suzuki, K. et al. Serine Protease Inhibitors Inhibit Superoxide Release and Adherence in Human Neutrophils Stimulated by Granulocyte-Macrophage Colony-Stimulating Factor and Tumor Necrosis Factor-α. Int J Hematol 77, 253–258 (2003). https://doi.org/10.1007/BF02983782

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Key words

  • Neutrophil
  • Cytokine
  • Superoxide
  • Adherence
  • Serine protease