Increased Prostaglandin Synthesis by Macrophages from Tumor-Bearing Mice

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Abstract
Prostaglandin E2 (PGE2) synthesis by macrophages was measured in normal and tumor-bearing mice. Splenic macrophages from C57BL mice bearing a transplantable, nonmetastasizing methylcholanthrene-induced fibrosarcoma produced significantly more PGE than cells from normal nontumor-bearing littermates. Augmented PG synthesis was found basally and after nonspecific stimulation of macrophages with endotoxin (LPS) and concanavalin A (Con A) as measured by radioimmunoassay. Resident peritoneal macrophages showed similar differences in radioimmunoassayable PGE levels. The conversion to prostaglandins of radiolabeled arachidonic acid previously incorporated into membrane phospholipids was followed over time. Macrophages from both normal and tumor-bearing animals incorporated equivalent amounts of tritiated arachidonic acid, showed similar distribution of label in phospholipid pools, and released equivalent amounts of labeled Arachidonic Acid and phospholipid. However, at both 3 and 18 hr of incubation, unstimulated macrophages from tumor-bearing animals released significantly more PGE2 and 6-keto PGF1α (the metabolite of prostacyclin) compared to macrophages from normal animals. Nonspecific stimuli (Con A and zymosan) greatly augmented PG production in both animal groups, with tumor-bearers greater than with normals. LPS caused little augmentation in basal PG secretion at 3 hr, but it greatly increased synthesis measured 18 hr later. In similar experiments, Moloney sarcoma virus (MSV) could be shown to augment PG synthesis in BALB/c mice bearing a transplantable MSV-transformed tumor line, but not in normal animals. No significant difference was noted in adherence, morphology, phagocytosis, or enzymatic activity when the resident macrophages from normal and tumor-bearing animals were compared, suggesting that they were at the same relative state of activation but differed in their capacity to synthesize prostaglandins.