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Tumor growth increases Ia- macrophage synthesis of tumor necrosis factor-alpha and prostaglandin E2: changes in macrophage suppressor activity.
J Leukoc Biol. 1993 May; 53(5):550-8.JL

Abstract

Although tumor growth enhances macrophage (m phi) cytotoxic activity by increasing their tumor necrosis factor-alpha (TNF-alpha) production, increased prostaglandin E2 (PGE2) synthesis reduces most immune responses during tumor growth. Macrophages that do not express major histocompatibility complex class II molecules (Ia- m phi) are the predominant suppressor and cytotoxic population and are more abundant in tumor-bearing hosts (TBHs). This study determined if TBH Ia- m phi s are the major population producing TNF-alpha and PGE2 and if these molecules affect Ia- m phi-mediated suppression of alloantigen-stimulated T cell proliferation. Normal host (NH) and TBH splenic Ia(+)-depleted (Ia-) m phi s synthesized more TNF-alpha than their respective whole populations (WPs) when cultured with lipopolysaccharide and interferon-gamma. TBH Ia- m phi s produced the most TNF-alpha. Northern blot analyses showed that Ia- m phi s had higher amounts of TNF-alpha mRNA expression than their respective WP, and TBH Ia- m phi s expressed the highest amounts of TNF-alpha mRNA. When WP and Ia- NH and TBH m phi s were added to alloantigen-stimulated T cells, suppression of T cell proliferation mediated by Ia- m phi s was greater than by their respective WP. TBH Ia- m phi s were most suppressive. The blockage of PGE2 production reduced suppression mediated by TBH Ia- m phi s more than by all other m phi populations. A PGE2-specific enzyme-linked immunosorbent assay showed that PGE2 production was greater in Ia- m phi- than in WP m phi-containing cultures and greatest in cultures containing TBH Ia- m phi s. Because TNF-alpha enhances T cell responses, its effects on Ia- m phi PGE2-mediated suppression was determined. When TNF-alpha was added to m phi-containing T cell cultures, TNF-alpha directly stimulated NH, but not TBH, Ia- m phi s, which enhanced T cell proliferation. However, inhibiting PGE2 production allowed TNF-alpha to stimulate T cell proliferation in TBH Ia- m phi-containing cultures. Collectively, these data show that Ia- m phi s are the major TNF-alpha- and PGE2-producing cells and that these molecules are partly responsible for the tumor-induced increase in m phi-mediated cytotoxicity and suppression, respectively. TNF-alpha not only mediates cytotoxicity but also counteracts Ia- m phi PGE2-mediated suppression. Although tumor growth increases Ia- m phi TNF-alpha production, enhanced PGE2 production blocks TNF-alpha's stimulatory action on Ia- m phi s, which favors their suppressor function during tumor growth.

Authors+Show Affiliations

Department of Biology, Virginia Polytechnic Institute and State University, Blacksburg 24061-0406.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

8388910

Citation

Alleva, D G., et al. "Tumor Growth Increases Ia- Macrophage Synthesis of Tumor Necrosis Factor-alpha and Prostaglandin E2: Changes in Macrophage Suppressor Activity." Journal of Leukocyte Biology, vol. 53, no. 5, 1993, pp. 550-8.
Alleva DG, Burger CJ, Elgert KD. Tumor growth increases Ia- macrophage synthesis of tumor necrosis factor-alpha and prostaglandin E2: changes in macrophage suppressor activity. J Leukoc Biol. 1993;53(5):550-8.
Alleva, D. G., Burger, C. J., & Elgert, K. D. (1993). Tumor growth increases Ia- macrophage synthesis of tumor necrosis factor-alpha and prostaglandin E2: changes in macrophage suppressor activity. Journal of Leukocyte Biology, 53(5), 550-8.
Alleva DG, Burger CJ, Elgert KD. Tumor Growth Increases Ia- Macrophage Synthesis of Tumor Necrosis Factor-alpha and Prostaglandin E2: Changes in Macrophage Suppressor Activity. J Leukoc Biol. 1993;53(5):550-8. PubMed PMID: 8388910.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Tumor growth increases Ia- macrophage synthesis of tumor necrosis factor-alpha and prostaglandin E2: changes in macrophage suppressor activity. AU - Alleva,D G, AU - Burger,C J, AU - Elgert,K D, PY - 1993/5/1/pubmed PY - 1993/5/1/medline PY - 1993/5/1/entrez SP - 550 EP - 8 JF - Journal of leukocyte biology JO - J. Leukoc. Biol. VL - 53 IS - 5 N2 - Although tumor growth enhances macrophage (m phi) cytotoxic activity by increasing their tumor necrosis factor-alpha (TNF-alpha) production, increased prostaglandin E2 (PGE2) synthesis reduces most immune responses during tumor growth. Macrophages that do not express major histocompatibility complex class II molecules (Ia- m phi) are the predominant suppressor and cytotoxic population and are more abundant in tumor-bearing hosts (TBHs). This study determined if TBH Ia- m phi s are the major population producing TNF-alpha and PGE2 and if these molecules affect Ia- m phi-mediated suppression of alloantigen-stimulated T cell proliferation. Normal host (NH) and TBH splenic Ia(+)-depleted (Ia-) m phi s synthesized more TNF-alpha than their respective whole populations (WPs) when cultured with lipopolysaccharide and interferon-gamma. TBH Ia- m phi s produced the most TNF-alpha. Northern blot analyses showed that Ia- m phi s had higher amounts of TNF-alpha mRNA expression than their respective WP, and TBH Ia- m phi s expressed the highest amounts of TNF-alpha mRNA. When WP and Ia- NH and TBH m phi s were added to alloantigen-stimulated T cells, suppression of T cell proliferation mediated by Ia- m phi s was greater than by their respective WP. TBH Ia- m phi s were most suppressive. The blockage of PGE2 production reduced suppression mediated by TBH Ia- m phi s more than by all other m phi populations. A PGE2-specific enzyme-linked immunosorbent assay showed that PGE2 production was greater in Ia- m phi- than in WP m phi-containing cultures and greatest in cultures containing TBH Ia- m phi s. Because TNF-alpha enhances T cell responses, its effects on Ia- m phi PGE2-mediated suppression was determined. When TNF-alpha was added to m phi-containing T cell cultures, TNF-alpha directly stimulated NH, but not TBH, Ia- m phi s, which enhanced T cell proliferation. However, inhibiting PGE2 production allowed TNF-alpha to stimulate T cell proliferation in TBH Ia- m phi-containing cultures. Collectively, these data show that Ia- m phi s are the major TNF-alpha- and PGE2-producing cells and that these molecules are partly responsible for the tumor-induced increase in m phi-mediated cytotoxicity and suppression, respectively. TNF-alpha not only mediates cytotoxicity but also counteracts Ia- m phi PGE2-mediated suppression. Although tumor growth increases Ia- m phi TNF-alpha production, enhanced PGE2 production blocks TNF-alpha's stimulatory action on Ia- m phi s, which favors their suppressor function during tumor growth. SN - 0741-5400 UR - https://www.unboundmedicine.com/medline/citation/8388910/Tumor_growth_increases_Ia__macrophage_synthesis_of_tumor_necrosis_factor_alpha_and_prostaglandin_E2:_changes_in_macrophage_suppressor_activity_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0741-5400&date=1993&volume=53&issue=5&spage=550 DB - PRIME DP - Unbound Medicine ER -