Prostaglandin synthesis inhibitors potentiate the BCG-induced augmentation of natural killer cell activity

D. E. Tracey, N. F. Adkinson

Research output: Contribution to journalArticlepeer-review

Abstract

We have previously reported that BCG induced a rapid and intense augmentation of murine peritoneal natural killer (NK) cell activity. A requirement for macrophages and for soluble NK-enhancing factors was also demonstrated. In the present report we show that BCG-induced peritoneal macrophages secreted large amounts of prostaglandin E2 (PGE2). In vitro, PGE2 inhibited both normal splenic NK cells and BCG-induced peritoneal NK cells at concentrations between 10-9 and 10-5 M, in contrast to the inactive PGF(2α) isomer. BCG-induced PGE2 synthesis was inhibited in vivo with the prostaglandin cyclo-oxygenase inhibitors indomethacin and aspirin. These drugs concommitantly potentiated the BCG-induced augmentation of peritoneal NK cells, although they had only marginal effects on normal NK activity in vivo or in vitro. Pretreatment of BCG-induced peritoneal exudate cells (BCG-PEC) in vitro with indomethacin or aspirin also potentiated the augmentation of normal splenic NK cells by BCG-PEC supernatants in vitro. With these inhibitors of prostaglandin synthesis, there was an inverse correlation, both in vitro and in vivo, between the levels of PGE2 secreted by BCG-induced macrophages and the augmentation of NK activity. Thus, the macrophage appears to play a central role in the regulation of NK activity in BCG-infected mice by way of secreting NK-ehancing factors and NK-inhibiting factors, including PGE2. Pharmacologic intervention to manipulate NK activity via control of the secretion of macrophage factors may prove useful in further enhancing the immunotherapeutic effects of BCG.

Original languageEnglish (US)
Pages (from-to)136-141
Number of pages6
JournalJournal of Immunology
Volume125
Issue number1
StatePublished - Jan 1 1980

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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