Differential effects of chronic monocyte depletion on macrophage populations.

The administration of the bone-seeking isotope, 89Sr, to mice results in severe monocytopenia without any apparent effect on the numbers of resident peritoneal macrophages (Mphi). An explanation for this dichotomy was sought by determining whether the residual blood monocytes were still an effective source of Mphi after 89Sr treatment. Stem cell enumeration showed that a 90% fall in bone marrow macrophage colony-forming cells after 89Sr was accompanied by a 10-fold rise in splenic M-CFC. Splenectomy performed before 89Sr treatment, however, resulted in little additional monocytopenia and had no affect on the numbers of resident peritoneal Mphi even when sampling was extended to 31 days, an interval beyond the accepted half-time for peritoneal Mphi. Intraperitoneal injections of thioglycollate or Corynebacterium parvum elicited few or no monocyte-Mphi during respective intervals of 4 and 7 days. Elicitation with thioglycollate was attempted in tritiated thymidine-labeled mice 26 days after 89Sr. Four days later only a 2-fold increase in labeled peritoneal Mphi was found in the 89Sr-treated mice compared with a 150-fold increase in the controls. Studies of the ectoenzymes 5'-nucleotidase, alkaline phosphodiesterase I, and leucine aminopeptidase in such elicitation experiments suggested that the observed changes in activities reflected the direct stimulation of resident Mphi rather than monocyte immigration. Overall, the results indicate that treatment with 89Sr distinguishes two large populations of Mphi on the basis of their dependence on bone marrow. Mphi of inflammation reflect the monocytopenia and are severely and rapidly depleted by such treatment. The maintenance of resident type Mphi, on the other hand, appears to be independent of both the state of the bone marrow and the level of monocytes in the blood.