Effect of indomethacin and aspirin on the TNF-alpha-induced priming and protein tyrosyl phosphorylation of human neutrophils.

K. Minakami, Y. Watanabe, M. Miyahara, H. Kobuchi, T. Kurashige, K. Utsumi

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Receptor-mediated superoxide (O2-.)-generation in human peripheral neutrophils (HPPMN) is enhanced by various priming agents, such as granulocyte colony stimulating factor (G-CSF) and tumor necrosis factor (TNF-alpha). We previously reported that this enhancement occurred in parallel with the priming agent-induced increase in protein tyrosyl phosphorylation which is sensitive to tyrosine kinase (TK) inhibitors [Akimaru K. et al. Arch. Biochem. Biophys. 298:703, 1992]. We describe here that nonsteroidal anti-inflammatory drugs (NSAIDs) such as indomethacin and aspirin, modulate the priming and tyrosine phosphorylation of HPPMN. The enhancement by TNF-alpha of formylmethionyl-leucyl-phenylalanine (FMLP)-induced O2-. generation was not inhibited by 5 microM azide, whereas that of FMLP-induced luminol chemiluminescence (LCL) was sensitive. Enhancement of FMLP-induced O2-. generation and LCL by priming agents was inhibited by both aspirin and indomethacin in a concentration dependent manner. This inhibition by the NSAIDs was much stronger than that for FMLP-induced O2-. generation without priming. The half-inhibition dose of indomethacin and aspirin were 50 microM and 1.5 mM, respectively. The priming-induced enhancement of tyrosyl phosphorylation of some neutrophil proteins, such as that of 108 and 115 kDa, was also inhibited by aspirin and indomethacin in a dose-dependent manner. However, dose dependent inhibition of the enhanced O2-. generation by the NSAIDs was not completely similar to that of enhanced tyrosyl phosphorylation. However, PKC-mediated O2-. generation, which has little sensitivity to TNF-alpha or G-CSF, was rather stimulated by the NSAIDs. These findings suggest that aspirin and indomethacin inhibit also the early steps of neutrophil activation as reflected by their ability to inhibit priming and the related tyrosyl phosphorylation of neutrophil proteins.

Original languageEnglish
Pages (from-to)55-67
Number of pages13
JournalPhysiological chemistry and physics and medical NMR
Volume25
Issue number1
Publication statusPublished - 1993
Externally publishedYes

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Physiology
  • Spectroscopy

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