Prostaglandin E2 production by Mac-2+ macrophages: Tumor-induced population shift

A. P. Malick, K. D. Elgert, R. E. Garner, N. F. Adkinson

Research output: Contribution to journalArticle

Abstract

Tumor growth induced a shift in the phenotype of macrophages (M∅) responsible for factor-mediated suppression of allogeneic mixed lymphocyte reactions (MLR), and the suppression by tumor-bearing host (TBH) Mac-2+ M∅ was in part due to production of prostaglandin E2 (PGE2). Thioglycollate-elicited peritoneal M∅ from normal and TBH BALB/c mice were modulated with anti-Mac-1, -2, or -3 monoclonal antibodies (mAb) or depleted with mAb plus complement and cultured in the presence or absence of indomethacin. Culture supernatants derived from mAb plus complement-depleted M∅ were added to the MLR at time of initiation and showed that the suppressor phenotype shifted from Mac-3+ in the normal host to Mac-2+ in the TBH. Mac-1+ M∅ also appeared to be involved in suppression by normal host, but not TBH, M∅. Loss of MLR suppression (increase in MLR reactivity) correlated with an increase in protein content of the culture supernatants. In an effort to explain both this relationship and the mechanism of MLR supression, PGE2 levels of culture supernatants were determined by radioimmunoassay. Mac-1+ M∅ were involved in the regulation of PGE2 production in normal hosts, as both activation and depletion caused an increase in PGE2 production. Depletion caused a more dramatic increase in PGE2 production than did activation, suggesting that MAC-1+ M∅ had a dampening effect on PGE2 production. In contrast, no Mac-1+ M∅-mediated regulatory function occurred in the TBH. Mac-3+ M∅ were involved in the regulation of PGE2 production in both normal and TBH. Mac-2+ M∅ were the primary producers of PGE2 in the TBH, but not in the normal host, as their depletion in the TBH caused a significant loss of PGE2 production. Thus, immunosuppression in the TBH was at least partly due to the inability of Mac-1+ and/or Mac-3+ M∅ to control production of PGE2 by Mac-2+ M∅.

Original languageEnglish (US)
Pages (from-to)673-681
Number of pages9
JournalJournal of Leukocyte Biology
Volume42
Issue number6
DOIs
StatePublished - Jan 1 1987
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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