Oxidative stress triggers tyrosine phosphorylation in B cells through a redox- and inflammatory cytokine-sensitive mechanism.
Exposure to oxidants such as hydrogen peroxide (H2O2) and gamma-ray irradiation has been recently shown to trigger tyrosine phosphorylation in B cells as does cross-linking surface immunoglobulin (sIg) by antigens or anti-immunoglobulins. We studied the mechanism by which H2O2 induced tyrosine phosphorylation in B cells and compared it with the mechanism utilized by sIg. Both anti-immunoglobulin M (anti-IgM) and H2O2 induced tyrosine phosphorylation through protein tyrosine kinase (PTK) activation. However, the tyrosine phosphorylation caused by H2O2 but not that induced by anti-IgM, was modulated by agents affecting cellular thiols and glutathione contents including dithiothreitol, 2-mercaptoethanol, and buthionine sulphoximine. Moreover, the tyrosine phosphorylation caused by the oxidant but not that induced by anti-IgM was markedly augmented by two inflammatory cytokines, tumour necrosis factor-alpha and interleukin-1 alpha, although these agents by themselves did not stimulate PTK activity nor induce tyrosine phosphorylation. These findings demonstrate that oxidative stress but not surface IgM (sIgM) ligation triggers tyrosine phosphorylation through a mechanism that is sensitive to cellular thiols and these inflammatory cytokines.
Suzuki
Y
Y
Department of Microbiology, Nihon University School of Medicine, Tokyo, Japan.
Ohsugi
K
K
Ono
Y
Y
D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D016207:Cytokines / Q000494:pharmacology*; D004789:Enzyme Activation; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007075:Immunoglobulin M; D007375:Interleukin-1 / Q000494:pharmacology; D008213:Lymphocyte Activation; D010084:Oxidation-Reduction; D010085:Oxidative Phosphorylation; D018384:Oxidative Stress / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014443:Tyrosine / Q000378:metabolism*
D000888:Antibodies, Anti-Idiotypic; D016207:Cytokines; D007075:Immunoglobulin M; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D014443:Tyrosine; D006861:Hydrogen Peroxide; D011505:Protein-Tyrosine Kinases