The divergent effects of endotoxin fractions on human plasma and leukocytes.
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Biomedical subjects
Publications and source records attributed to K L Melmon.
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Prostaglandins E(1) and E(2) (PGE(1) and PGE(2)) stimulate adenyl cyclase activity in broken cell preparations of normal human leukocytes, whereas prostaglandin F(1a) produces no effect. PGE(1) and PGE(2) also cause increased accumulation of cyclic 3',5'-adenosine monophosphate-(3)H ((3)H-labeled AMP) in intact leukocytes which have been preincubated with adenine-(3)H in vitro. Theophylline inhibits leukocyte phosphodiesterase activity and potentiates the stimulatory effect of the prostaglandins on intracellular accumulation of cyclic 3',5'-AMP-(3)H. The ability of human granulocytes in vitro to kill Candida albicans was consistently inhibited by PGE(1) and theophylline. This effect was reproduced by dibutyryl cyclic 3',5'-AMP, a lipid-soluble analogue of the endogenous nucleotide. The inhibition of candidacidal activity could not be accounted for by drug effects on phagocytosis, oxygen consumption, or hexose monophosphate shunt activity. These results are consistent with the hypothesis that increased intracellular concentrations of cyclic 3',5'-AMP impair the granulocyte's ability to kill C. albicans, but the precise mechanism of inhibition has not yet been defined.
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The concentrations of free tyrosine in liver, muscle, kidney and thyroid gland were determined in separate groups of rats maintained on a low iodine diet and treated with intraperitoneal injections of thyroxine (T 4), thyrotrophin (TSH) and TSH plus propylthiouracil (PTU). Groups of hypophysectomized rats also were given T 4. Significant changes in tissue tyrosine were generally confined to the thyroid gland. Animals treated with T 4 showed a decrease of mean thyroid tyrosine from 113.3 +/- 17.9 (S.D.) mug/g wet weight of gland to 76.2 +/- 5.7 mug/g (P < 0.01). Although there was little change in content when TSH was given alone, a significant increase in tyrosine levels was observed when TSH plus PTU were administered (P < 0.01). In hypophysectomized rats thyroid tyrosine decreased and was further lowered (to 46.0 +/- 3.1 mug/g; P < 0.05) by T 4 treatment. When tyrosine concentrations were expressed in relation to ribonucleic acid (RNA) or protein content of the assayed gland, all differences in tyrosine content became greater.
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