Increased activity of FIM in serum of mice during a Mycobacterium bovis (BCG) infection.

In mice given an intravenous injection of Mycobacterium bovis (BCG), the bacilli proliferated in the spleen, liver and lungs but the peritoneal cavity remained sterile. The numbers of blood monocytes and alveolar macrophages were increased during the first 2 weeks of the infection, whereas the number of peritoneal macrophages remained constant. To study whether factor-increasing monocytopoiesis (FIM) plays a role in the regulation of the monocytosis during the BCG infection, the activity of this factor in the serum of mice at various intervals during the infection was determined. Previous studies have shown that FIM stimulates monocyte production by its effect on the mitotic activity of monoblasts and promonocytes in the bone marrow. The FIM activity of the serum reached a maximum on Day 4 and remained elevated during the first 21 days of the BCG infection. Since FIM is synthesized and secreted by macrophages that have phagocytosed opsonized particles, it is highly probable that FIM occurring in serum originates from macrophages that have ingested BCG. The results of the present study led to the conclusion that FIM plays a role in the monocytosis developing during infection with BCG.

Macrophages as origin of factor increasing monocytopoiesis.

Earlier investigations had indicated that the factor increasing monocytopoiesis (FIM), present in the serum of mice and rabbits during the onset of an inflammatory response, is released by cells of the inflammatory exudate. The present study was performed to determine which cells produce and secrete this factor and to establish the kinetics of its production and secretion. FIM was assayed in vivo by intravenous injection of samples into untreated mice and monitoring the course of the number of blood monocytes in the recipients. FIM was assayed in vitro by adding samples to cultures of the macrophage cell line PU5 and determining the rate of proliferation of the cells. The results show that only macrophages contain and synthesize FIM. This factor is secreted upon exposure to a phagocytic stimulus, and after the release of preformed FIM, macrophages secrete newly synthesized FIM. Granulocytes and lymphocytes neither contain nor secrete FIM. The characteristics of FIM derived from macrophages are in all aspects similar to those of FIM in serum. Macrophage-derived FIM is a protein with a molecular weight between 10 and 25 X 10(3), its activity is cell-lineage specific and dose dependent, and it stimulates monocyte production in the bone marrow. Macrophage-derived FIM is not identical to either CSF-1 or IL-1, and has no chemotactic activity. Taken together, the present results show that FIM occurring in serum during an inflammatory response originates from macrophages at the site of the inflammation. In this way the macrophages themselves regulate the supply of circulating blood monocytes that can migrate to the site of injury when needed.