Deoxycytidine excretion by mouse peritoneal macrophages: its implication in modulation of immunological functions

Abstract

Pyrimidine excretion by macrophages was studied in order to identify the potential immunoregulatory effector molecules. Deoxycytidine was found in the culture medium of thioglycollate-elicited mouse peritoneal macrophages, along with thymidine, which was shown by others to be a possible immunoregulatory substance. The identification of deoxycytidine was based on: (1) cochromatography with the authentic compound in four different solvents, (2) UV absorption spectral analysis, and (3) the enzymatic peak shift method. Phagocytosis of nucleated chicken erythrocytes, but not enucleated sheep erythrocytes, increased deoxycytidine excretion. The macrophages lacked both deoxycytidine kinase and deoxycytidine deaminase, which is consistent with their excretory pattern. Since it has been known that deoxycytidine can protect cells against cytotoxic effects of thymidine, we propose that deoxycytidine has a role in preventing immunosuppression by thimidine. In patients with adenosine deaminase deficiency, however, immunosuppression caused by combined toxicity of thymidine and deoxyadenosine may not be adequately prevented by deoxycytidine.