Production of the effector molecule thymidine by human lung alveolar macrophages

Cultured human alveolar macrophages (HAMØ) were found to produce soluble factors which inhibit tritiated thymidine ([3H]-TdR) incorporation into tumour cells in vitro. We present evidence that thymidine (TdR) can be detected in HAMØ culture supernatants by thin-layer chromatography. Moreover, TdR secretion by HAMØ is an active process. Using [6-14C]-orotic acid as an early precursor to TdR and [3H]-TMP as the phosphorylation product, we were able to show that cultured HAMØ transformed them into labelled TdR. The very efficient thin-layer chromatography of the labelled metabolites was backed up by high-pressure liquid chromatography of nucleotides. HAMØ produce TdR by de novo synthesis and dephosphorylation. This phenomenon is due to the lack of thymidine kinase in normal mature macrophages. Since TdR, in high concentrations, can inhibit DNA synthesis through the 'TdR blockade' phenomenon, it is suggested that TdR secretion by HAMØ is a mechanism of non-specific modulation of tumour cell growth but highly restricted to the immediate macrophage microenvironment in vivo. The effectiveness of the thymidine gradient may thus be quite narrow, but is worthy of interest. © 1984.SCOPUS: ar.j