Depression of Murine Macrophage Accumulation by Low-Molecular-Weight Factors Derived From Spontaneous Mammary Carcinomas

Abstract

Extracts prepared from spontaneous mouse mammary adenocarcinomas, as well as plasma and urine from inbred C3H/HeN mice carrying murine mammary tumor virus and bearing such tumors, significantly inhibited the accumulation of macrophages at inflammatory sites in inbred C3Heb/FeJ mice. Much of the inhibitory activity from tumor cells was associated with products having a low molecular weight (<30,000); the inhibitory factor isolated from the plasma and urine of tumor-bearing animals had a molecular weight of 30,000 or less. Liver and spleen tissue, plasma, and urine from non-tumor-bearing animals had no effect on macrophage accumulation. Tumor cell extracts, plasma, and urine from tumor-bearing mice were shown to be free of infectious lactate dehydrogenase virus, a frequent contaminant of transplanted tumors and a known modifier of macrophage function. These results agreed with earlier reports of inhibitory activity for macrophage accumulation found in the tumors and sera of mice bearing multiple-passaged transplanted tumors and suggested that spontaneously arising neoplasms may subvert immune surveillance by depressing the ability of macrophages to respond to inflammatory stimuli.