A dual origin, by both immigration of blood monocytes and local prolif
eration has been reported for macrophages, which are heterogeneous in
several aspects. Until now few studies have focussed on renewal of mac
rophages. Therefore, in this study macrophage renewal by local prolife
ration has been studied in the spleen. Spleen tissue of mice which had
received BrdU intravenously was investigated immunohistochemically to
detect BrdU incorporated by macrophages. BrdU incorporation by spleni
c macrophages was studied under steady state conditions as well as dur
ing repopulation after experimental macrophage depletion. Under steady
state conditions, BrdU incorporation was found in 3.0 +/- 0.5% of the
white pulp macrophages and in approximately 1% of the metallophilic m
acrophages only. Comparable results were found during repopulation aft
er experimental macrophage depletion. The data suggest that renewal of
macrophages by local proliferation is restricted to certain subsets i
n the spleen and that the macrophage subsets of the spleen are renewed
by different mechanisms, or belong to different lineages of macrophag
e differentiation.