Macrophage anti‐tumor functions in a chicken MHC chromosome dosage model

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Abstract
We compared the capacity of chicken inflammatory macrophages differing in dosage of the MHC‐containing microchromosome (aneuploids) for anti‐tumor cell function. Sephadex‐elicited avian peritoneal macrophages possessing two (disomic), three (trisomic), or four (tetrasomic) copies of chromosome no. 16 were tested for anti‐tumor cell activity against a reticuloendotheliosis virus‐transformed target cell (RECC‐CU60). Aneuploid macrophages collected 24 hours post‐Sephadex exhibited an enhanced anti‐tumor cell activity compared with disomic cells (5:1 effector‐to‐target ratio); similarly, tetrasomic macrophages collected 42 hours post injection also possessed an elevated activity for tumor cell reduction vs. disomic macrophages. However, when macrophages and tumor cells were co‐cultured with a microfilter barrier insert or when macrophage‐conditioned medium was used, no significant differences were observed among genotypes. This suggests that cell contact is a component of the observed macrophage anti‐tumor cell function influenced by MHC dosage. Because aneuploid macrophages are altered in reactive oxygen intermediate (ROI) production, the possible role of ROIs and the reactive nitrogen intermediates (RNIs) was examined. MHC dosage‐based differences in macrophage RNI production were not associated with the differential anti‐tumor capacity. H2O2 was shown to be a potential anti‐tumor metabolite in this culture system; however, enhanced tumor cell capture and/or contact‐dependent delivery of macrophage metabolites may be more important than differential metabolite production in explaining the genetic differences in anti‐tumor function.