TUMORICIDAL PROPERTIES OF INFLAMMATORY TISSUE MACROPHAGES AND MULTINUCLEATE GIANT-CELLS

  • 1 January 1979
    • journal article
    • research article
    • Vol. 96  (2) , 595-610
Abstract
Peritoneal exudate cells from C3H/HeN mice infected with BCG and subcutaneous inflammatory macrophages from uninfected mice exhibit spontaneous cytotoxicity for tumor cells in vitro but their tumoricidal activity can be increased by incubation in vitro with lymphokines released by mitogen- or antigen-stimulated lymphocytes. Inflammatory macrophages from these sites are only susceptible to activation in vitro by lymphokines for a short period (< 4 days) following their initial emigration from the circulation to the site of inflammation. The expression of tumoricidal activity by activated macrophages is similarly short-lived (< 4 days). Once the tumoricidal state is lost it cannot be restored by further incubation with lymphokines in vitro. Fusion of macrophages to form multinucleate giant cells (MGC) accompanies the loss of tumoricidal activity and the onset of resistance to activation by lymphokines, but the fusion process is not responsible for these changes since unfused macrophages are similarly affected. Activation and acquisition of tumoricidal properties is confined to young macrophages recruited from the the circulation during acute inflammation. Older macrophages and MGC in chronic inflammatory lesions in which recruitment of new macrophages has ceased are non-tumoricidal and are refractory to activation by lymphokines in vitro. The efficiency of macrophage-mediated destruction of tumors in vivo and the amplification of macrophage anti-tumor activity by immunotherapeutic agents are discussed.