Natural killer cell activity, lymphocyte proliferation, and cytokine profile in tumor-bearing mice treated with MAPA, a magnesium aggregated polymer from Aspergillus oryzae

Immunopharmacol Immunotoxicol. 2003 Aug;25(3):305-19. doi: 10.1081/iph-120024499.

Abstract

The present study examined the effects of MAPA, an antitumor aggregated polymer of protein magnesium ammonium phospholinoleate-palmitoleate anhydride, isolated from Aspergillus oryzae, on concanavalin A (Con A)-induced spleen cell proliferation, cytokine production and on natural killer (NK) cell activity in Ehrlich ascites tumor-bearing mice. The Ehrlich ascites tumor (EAT) growth led to diminished mitogen-induced expansion of spleen cell populations and total NK activity. This was accompanied by striking spleen enlargement, with a marked increase in total cell counts. Moreover, a substantial enhancement in IL-10 levels, paralleled by a significant decrease in IL-2 was observed, while production of IL-4 and interferon-gamma (IFN-gamma) was not altered. Treatment of mice with 5 mg/kg MAPA for 7 days promoted spleen cell proliferation, IL-2 production and NK cell activity regardless of tumor outgrowth. In addition, MAPA treatment markedly enhanced IFN-gamma levels and reduced IL-10 production relative to EAT mice. A 35% reduction in splenomegaly with normal number of nucleated cells was also found. Altogether, our results suggest that MAPA directly and/or indirectly modulates immune cell activity, and probably disengages tumor-induced suppression of these responses. Clearly, MAPA has an impact and may delay tumor outgrowth through immunotherapeutic mechanisms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / isolation & purification
  • Antineoplastic Agents / pharmacology*
  • Aspergillus oryzae* / chemistry
  • Carcinoma, Ehrlich Tumor / drug therapy*
  • Carcinoma, Ehrlich Tumor / immunology
  • Carcinoma, Ehrlich Tumor / pathology
  • Cell Proliferation / drug effects*
  • Cells, Cultured
  • Concanavalin A / pharmacology
  • Cytokines / metabolism*
  • Killer Cells, Natural / drug effects*
  • Killer Cells, Natural / immunology
  • Linoleic Acids / isolation & purification
  • Linoleic Acids / pharmacology*
  • Lymphocytes / drug effects*
  • Lymphocytes / immunology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mitogens / pharmacology
  • Organophosphorus Compounds / isolation & purification
  • Organophosphorus Compounds / pharmacology*
  • Spleen / drug effects*
  • Spleen / immunology
  • Spleen / pathology
  • Splenomegaly / immunology
  • Splenomegaly / prevention & control
  • Time Factors
  • Tumor Escape / drug effects

Substances

  • Antineoplastic Agents
  • Cytokines
  • Linoleic Acids
  • Mitogens
  • Organophosphorus Compounds
  • magnesium ammonium phospholinoleate anhydride
  • Concanavalin A