PGE2 receptors on murine splenic lymphocytes: effects of tumor bearing.
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)
Elkashab
M
M
Department of Anatomy, University of Western Ontario, London, Canada.
Lala
P
P
D000230:Adenocarcinoma / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D005260:Female; D007700:Kinetics; D008214:Lymphocytes / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D009368:Neoplasm Transplantation; D011458:Prostaglandins E / Q000378:metabolism; D011863:Radioimmunoassay; D011982:Receptors, Prostaglandin / Q000378:metabolism*; D018078:Receptors, Prostaglandin E; D013154:Spleen / Q000378:metabolism*
D011458:Prostaglandins E; D011982:Receptors, Prostaglandin; D018078:Receptors, Prostaglandin E