Effects of native and heat-denatured Abrus agglutinin on tumor-associated macrophages in Dalton's lymphoma mice

Tumor-associated macrophages (TAMs) have a complex and ambivalent relationship with tumor progression and elimination. Though TAMs are reported to have pro- and anti-tumor roles, upon modification and activation TAMs can develop tumoricidal activities and thus might have applications in cancer therapy. Various immunomodulatory compounds could be used to modulate TAMs. In this study we used Abrus agglutinin, a plant lectin, in its native and heat-denatured forms, to investigate its effect on TAMs in Dalton's lymphoma-bearing mice. We found that treatment with both native (NA) and heat-denatured agglutinin (HDA) activated the TAMs, which showed significantly increased in vitro cytotoxicity towards tumor cells and production of nitric oxide but no difference in TNF-alpha production. The tumoricidal activities of both NA and HDA were dependent upon the activation of TAMs as in macrophage-depleted Dalton's lymphoma-bearing mice NA and HDA treatment could not decrease the number of tumor cells significantly. Thus, NA and HDA could be used as modulators of TAMs, for their therapeutic use in cancer. (C) 2007 Elsevier GmbH. All rights reserved.