Effect of phospholipase A2 inhibitors on mouse T lymphocytes. I. Phospholipase A2 inhibitors exert similar immunological activities as glycosylation inhibiting factor

Hlroyuki Ohno, Makoto Iwata, Tsutomu Nakamura, Kimishige Ishizaka

Research output: Contribution to journalArticle

Abstract

Since our previous experiments suggested that gtycosylation-inhibiting factor (GIF) is a phosphorylated derivative of a phosphollpase inhibitory protein, we determined whether other well-known phosphollpase inhibitors may have similar biological activities. The results showed that phosphollpase A2 (PLA2) inhibitors, such as recombinant human lipocortin I and ONO-RS-082, could switch T cell hybridoma 12H5 cells from the formation of glycosylated IgE-binding factors (IgE-BF) to the formation of unglycosylated IgE-BF, whereas neomycin, a phospholipase C inhibitor, failed to affect the nature of IgE-BF formed by the cells. The minimum concentrations of lipocortin I and ONO-RS-082 required for switching the 12H5 cells to the formation of unglycosylated IgE-BF were comparable to or less than IC50 of the inhibitors for PLA2 The ability of partially purified GIF to switch the 12H5 cells to the formation of unglycosylated IgE-BF was markedly enhanced by treatment of the preparation with alkaline phosphatase. It was also found that lipocortin I and ONO-RS-082, but not neomycln, facilitated the generation of GIF-producing T cells. When spleen cells of ovalbumin (OVA)-primed BDF1 mice were stimulated with homologous antigen and the activated T cells were propagated by recombinant IL-2 in the presence of GIF, Iipocortin I, or ONO-RS-082, I cells obtained In the cultures constltutively produced their own GIF. Antigenic stimulation of the T cells Induced the formation of unglycosylated IgE-BF and GIF with an affinity for OVA. In contrast, the same antigen-activated T cells which had been propagated in the absence of PLA2 Inhibitor constitutively secreted glycosylatation-enhancing factor and formed glycosylated IgE-BF upon antigenic stimulation. The results Indicate that PLA2 Inhibitory activity of GIF is responsible for its immunological activities.

Original languageEnglish (US)
Pages (from-to)425-433
Number of pages9
JournalInternational Immunology
Volume1
Issue number4
DOIs
Publication statusPublished - Sep 1989

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Keywords

  • Antigen-specific suppressor factor
  • IgE-binding factors
  • Suppressor T cell circuit

ASJC Scopus subject areas

  • Statistics, Probability and Uncertainty
  • Applied Mathematics
  • Public Health, Environmental and Occupational Health
  • Neuropsychology and Physiological Psychology
  • Transplantation
  • Immunology

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