The aim of this study was to clarify the effects of α-N-acetylgalactosaminidase (α-NaGalase) produced by human salivary gland adenocarcinoma (SGA) cells on the bioactivity of macrophage-activating factor (GcMAF). High exo-α-NaGalase activity was detected in the SGA cell line HSG. HSG α-NaGalase had both exo- and endo-enzyme activities, cleaving the Gal-GalNAc and GalNAc residues linked to Thr/Ser but not releasing the [NeuAc2-6]GalNac residue. Furthermore, GcMAF enzymatically prepared from the Gc protein enhanced the superoxide-generation capacity and phagocytic activity of monocytes/macrophages. However, GcMAF treated with purified α-NaGalase did not exhibit these effects. Thus, HSG possesses the capacity to produce larger quantities of α-NaGalase, which inactivates GcMAF produced from Gc protein, resulting in reduced phagocytic activity and superoxide-generation capacity of monocytes/macrophages. The present data strongly suggest that HSG α-NaGalase acts as an immunodeficiency factor in cancer patients.

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