KINETICS AND DOSE DEPENDENCE OF MACROPHAGE-COLONY-STIMULATING FACTOR-INDUCED PROLIFERATION AND ACTIVATION OF MURINE MONONUCLEAR PHAGOCYTES IN-SITU - DIFFERENCES BETWEEN LUNGS, LIVER, AND SPLEEN

Alveolar macrophages (AM) play an important role in antimicrobial defe nse mechanisms of the lung, It therefore seems reasonable to use macro phage colony-stimulating factor (M-CSF) to enhance local resistance me chanisms, However, little is known about the in vivo activity of M-CSF on macrophages in various organs, We determined the effect of a singl e subcutaneous dose of M-CSF (10, 50, 100, and 500 ng, respectively) o n the number and functional status of AM as well as of macrophages in liver and spleen of mice, Organs were investigated immunohistochemical ly on days 1 and 3 after injection using monoclonal antibodies specifi c for F4/80, Ia antigen, and MAC-1. We found a significant increase in the number of F4/80(+) AM, Kupffer cells, and splenic macrophages rea ching its maximum 24 h after injection of low doses (10 and 50 ng per mouse, respectively) of M-CSF and decreasing to a level seen in untrea ted mice at 72 h after M-CSF in liver and spleen, whereas at a dose of 50 ng per mouse the number of AM remained high, In contrast, the numb ers of AM, Kupffer cells, and splenic macrophages did not increase sig nificantly when high doses were used (500 ng), The expression of Ia an tigen and MAC-1 was increased on macrophages in the spleen but not on AM or Kupffer cells. TNF-alpha was elevated in bronchoalveolar (BAL) f luid after 3 h and IL-6 at 6, 12, and 24 h after M-CSF injection in a dose-dependent manner, Nitric oxide production was not increased after injection of M-CSF. Our results point to regional differences in the response of macrophages to M-CSF, These may be caused by differences i n the M-CSF-induced production of TNF-alpha and IL-6. These findings m ay be important for the therapeutic use of M-CSF in microbial infectio ns.