Earlier studies from this laboratory revealed that killer lymphocyte lineages are inactivated in the
tumor-bearing host by macrophage-derived
PGE2. In this study, we examined whether
tumor bearing causes a change in the density or affinity of
PGE2 receptors on lymphocytes, making them more vulnerable to
PGE2 action, and whether it enhances
PGE2 production by host macrophages.
PGE2 receptors were examined on both unfractionated and monocyte-macrophage-depleted splenocytes of normal or
tumor-bearing C3H/HeJ mice (at 25 days following s.c.
transplantation of 10(6) C3 mammary
adenocarcinoma cells) using a [3H]
PGE2 binding assay in the presence of increasing (up to 10(4)-fold) concentrations of unlabeled
PGE2 (or
PGA or
PGF2 alpha as specificity controls) followed by a Scatchard analysis.
PGE2 production by splenic macrophages was measured with a radio-immunoassay. Results revealed that splenocytes in normal and
tumor-bearing mice bear specific receptors for
PGE2, since splenocyte binding of [3H]
PGE2 (10(-9) M) was inhibited in the presence of excess unlabeled
PGE2, but not 10(-4)-fold excess
PGA or
PGF2 alpha.
Tumor-bearing did not appear to cause an appreciable change in the affinity or density of these receptors, since Kd and Bmax values for
PGE2 binding were similar for normal and
tumor-bearing mice. However, specific PGE2-binding by splenocytes in vitro was reduced in
tumor-bearing mice. Three types of evidence indicate that this resulted from a partial occupation of
PGE2 receptors on lymphocytes with
PGE2 produced by splenic macrophages of
tumor-bearing hosts. First, depletion of monocyte-macrophages from the splenocyte population improved this binding in
tumor-bearing but not normal mice.(ABSTRACT TRUNCATED AT 250 WORDS)