Bone marrow colony-stimulating factor and tumor resistance-enhancing activity of postendotoxin mouse sera

Abstract

The passive transfer of postendotoxin mouse serum could enhance nonspecific resistance to the development of TA3-Ha transplantable ascites tumor in mice. The postendotoxin serum was not directly cytotoxic to TA3-Ha tumor cells in vitro, nor did it contain significant amounts of residual endotoxin, but it was rich in colony-stimulating factors (CSF). High-titer CSF serum could be induced by endotoxic lipopolysaccharide (LPS). Nonendotoxic, lipid-free and polysaccharide-rich hydrolytic breakdown product of LPS (called PS) was less potent but still active in CSF induction. There was a correlation between the level of CSF stimulation and the capacity of the sera to transfer tumor resistance (TUR). Those LPS preparations that had the highest CSF-inducing capacity were the most potent in TUR enhancement. Suppression of CSF production by treatment with theophylline or epinephrine, enhancers of cyclic[c]AMP/cGMP ratios, lowered the enhancement of TUR by endotoxic LPS. The infection of serum donor mice with BCG 18 days prior to LPS treatment gave the highest serum CSF levels and the most potent TUR-inducing serum preparation. Even more notable was the finding that the nontoxic PS preparation could replace toxic LPS in the above BCG-LPS system. The serum harvested from BCG-infected mice 2 h after PS injection was similarly effective in the passive transfer of TUR. [Endotoxins and derivatives from Serratia marcescens, Salmonella minnesota, S. typhimurium and Escherichia coli strains were used.].