Macrophage function in tumor-bearing mice: evidence for lactic dehydrogenase-elevating virus-associated changes.

Abstract

After transfer into normal mice, serum from mice bearing any one of six transplantable tumors induced abnormal macrophage phagocytic and chemotactic responses in vitro. Macrophages from normal mice treated with spleen, liver, or peritoneal cells from tumor-bearing mice also exhibited increased phagocytic and depressed chemotactic responsiveness; serum from these treated animals could, in turn, transfer defects in macrophage function to other normal mice. Transfer of cells from tumor or nontumor tissues or serum from tumor-bearing mice into normal mice produced significant elevations in serum lactate dehydrogenase (LDH) activity. This response is pathognomonic for LDH virus infection. Injection of serum from mice known to be infected with LDH virus into normal animals produced changes in macrophage function identical to those observed in tumor-bearing mice. The alterations in macrophage functions subsequent to inoculation of tumor cells or LDH virus followed identical time courses and were detectable after serial transfer of serum mouse-to-mouse. In addition, phagocytic responses by macrophages from mice with LDH virus-negative tumors (tissue culture-passaged tumors, carcinogen-induced tumors within five transplant generations of the primary tumor or primary mammary tumors of female mice) were entirely normal. However, macrophage chemotactic responses of cells from mice with LDH virus negative tumors were depressed. We have, therefore, documented that although many of the changes in macrophage function previously described in tumor-bearing mice were secondary to the effects of LDH virus infection, defects in macrophage chemotactic responsiveness persist in LDH virus-free conditions.