The course of the increased number of liver macrophages and the origin of these cells were studied after intravenous stimulation by zymosan, stilboestrol, or corynebacterium. The macrophages were isolated by digestion of the liver with pronase and DNAase.
Zymosan doubled the number of liver macrophages per gram of liver and led to a four- to five-fold increase in the number of blood monocytes, whereas stilboestrol induced a four-fold increase of liver macrophages and a two-fold increase of blood monocytes. Corynebacterium administration gave a two-fold rise in the number of liver macrophages and a six-fold increase of blood monocytes.
The in vitro labelling index of the liver macrophages showed a transient but marked increase after the administration of zymosan or stilboestrol, but returned to approximately normal values 4 days after the stimulus. Hydrocortisone given 48 h before zymosan prevented this increase in the in vitro labelling index of liver macrophages, thus demonstrating that the mononuclear phagocytes labelled in vitro had recently been recruited from the bone marrow to the liver.
Stimulation by stilboestrol or zymosan of mice labelled with [3H]-thymidine caused an increase in the number of labelled liver macrophages and blood monocytes as compared with the numerical course of the labelled Kupffer cells and monocytes in untreated mice. It may be concluded that this increase is attributable to the increased influx into the circulation of labelled monocytes from the bone marrow, which in turn migrate to the liver in larger numbers than are seen in the normal steady state. Local proliferation could not have been responsible for the increased number of labelled liver macrophages, because free [3H]-thymidine was no longer available when the stimulus was applied. Evidence supporting the bone marrow origin of the increased number of monocytes and liver macrophages after intravenous stimulation was provided by the course of the number of monocytes and liver macrophages in hydrocortisone-treated mice given zymosan as stimulus.