CSF-1 STIMULATES NUCLEOSIDE TRANSPORT IN S1-MACROPHAGES

We have examined nucleoside transport (NT) in a cell line derived from primary day 7 murine bone marrow macrophages (S1 macrophages) in resp onse to the macrophage growth factor, colony-stimulating factor 1 (CSF -1). Adenosine and uridine transport in quiescent Sl macrophages occur red primarily by two facilitated diffusional routes, one that was sens itive and one that was relatively resistant to the inhibitor nitrobenz ylthioinosine (NBMPR). Addition of CSF-1 to quiescent cultures resulte d in increased adenosine and uridine transport with biphasic kinetics with respect to the cell cycle. Basal NT activity was elevated (about twofold) within 15 min of CSF-1 addition, returned to near basal level s by 1 h, and then increased again (three- to fourfold) 8-12 h later, returning again to basal levels by 48 h post CSF-1 stimulation. We pro pose that the large increase in NT activity at 8-12 h corresponded wit h the time when cultures synchronously began to enter the S phase of t he cell cycle. In addition to these changes in the absolute rates, the proportions of NBMPR-sensitive and NBMPR-insensitive transport also c hange after CSF-1 addition. Quiescent cultures exhibited primarily NBM PR-insensitve transport while logrithmically growing cultures exhibite d primarily NBMPR-sensitive nucleoside transport activity. The increas e in the NBMPR-sensitive component of the transport process paralleled a similar increase in the number of high-affinity NBMPR binding sites , suggesting that the mechanism for upregulating NBMPR-sensitive NT ac tivity involves increases in the number of NBMPR-sensitive transporter sites. Interestingly, we were unable to detect Na+-dependent concentr ative uptake of adenosine, uridine, or formycin-B either in the S1 mac rophage cell line or in primary (day 7) murine macrophages. Thus these bone marrow derived macrophages did not display the characteristicall y large Na+-dependent transport systems observed by others in peritone al macrophages, implying that these two populations of macrophages are , indeed, functionally distinct.