Polymorphonuclear neutrophils and T lymphocytes: strange bedfellows or brothers in arms?

Nitric oxide dysfunction in the pathophysiology of preeclampsia.

Complex regulation of T cell functions during pregnancy is required to ensure maternofetal tolerance. Here we reveal a novel pathway for the temporary suppression of maternal T cell responses in uncomplicated human pregnancies. Our results show that arginase activity is significantly increased in the peripheral blood of pregnant women and remarkably high arginase activities are expressed in term placentae. High enzymatic activity results in high turnover of its substrate L-arginine and concomitant reduction of this amino acid in the microenvironment. Amino acid deprivation is emerging as a regulatory pathway of lymphocyte responses and we assessed the consequences of this enhanced arginase activity on T cell responses. Arginase-mediated L-arginine depletion induces down-regulation of CD3f, the main signalling chain of the TCR, and functional T cell hyporesponsiveness. Importantly, this arginase-mediated T cell suppression was reversible, as inhibition of arginase activity or addition of exogenous L-arginine restored CD3f chain expression and T cell proliferation. Thus, L-arginine metabolism constitutes a novel physiological mechanism contributing to the temporary suppression of the maternal immune response during human pregnancy.

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Arginase activity mediates reversible T cell hyporesponsiveness in human pregnancy

Publisher Summary This chapter investigates the links between polyamines and tumors. It is particularly interesting to modify the culture conditions to clarify the influence of the environmental milieu on the activities of the polyamine biosynthetic enzymes by enhancing or decreasing the levels of these enzymes to see the role of polyamines in the cell growth process. To this purpose, several studies have been carried out with rat hepatoma cells growing in culture. Studies of the effects of growth conditions on ornithine decarboxylase (ODC) activity presents evidence that dilution of high-density hepatoma cell cultures with fresh medium results in a very large and transient increase in enzyme activity. Furthermore, among the factors affecting the growth conditions of the cultured cells, the addition of fresh medium or serum to the culture has been demonstrated to be one of the most important for a variety of other cell lines. In spite of the decades of research, most of the role of polyamines in eliciting the peculiar neoplastic behavior and in permitting invasive neoplastic growth remains unclear.

Polyamines in mammalian tumors. Part I.

Placental metabolism and its regulation in health and diabetes

1. The presence of S -adenosylmethionine decarboxylase in human prostate gland is reported. A satisfactory radiochemical enzymic assay was developed and the enzyme was partially characterized. 2. Putrescine stimulates the reaction rate by up to 6-fold at pH7.5: the apparent activation constant was estimated to be 0.13mm. The stimulation is pH-dependent and a maximal effect is observed at acid pH values. 3. Putrescine activation is rather specific: other polyamines, such as spermidine and spermine, did not show any appreciable effect. 4. The apparent K m for the substrate is 4×10 −5 m. The calculated S -adenosylmethionine content of human prostate (0.18μmol/g wet wt. of tissue) demonstrates that the cellular amounts of sulphonium compound are saturating with respect to the enzyme. 5. The enzyme is moderately stable at 0°C and is rapidly inactivated at 40°C. The optimum pH is about 7.5, with one-half of the maximal activity occurring at pH6.6. 6. Several carboxy - 14 C-labelled analogues and derivatives of S -adenosylmethionine were tested as substrates. The enzyme appears to be highly specific: the replacement of the 6′-amino group of the sulphonium compound alone results in a complete loss of activity. 7. Inhibition of the enzyme activity by several carbonyl reagents suggests an involvement of either pyridoxal phosphate or pyruvate in the catalytic process. 8. The inhibitory effect of thiol reagents indicates the presence of ‘essential’ thiol groups.

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S-Adenosylmethionine decarboxylase from human prostate. Activation by putrescine

Automated chromatographic analysis of human placenta polyamines

Arginase was purified about 1800-fold from extracts of human full-term placenta; the enzyme appeared to be homogenous by disc electrophoresis and molecular-sieve chromatography. The mol. wt. determination by gel filtration and sodium dodecyl sulphate/polyacrylamide-gel electrophoresis yielded a value of 70000 for the most pure and the partially purified enzyme. The human placenta arginase is a metalloenzyme with an optimum pH of 9.1. The Km for L-arginine is 27 mM. L-Ornithine and L-lysine show competitive inhibition with Ki values of 6.3 and 14 mM respectively.

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Gennaro Della Pietra

Papers

S-Adenosylmethionine decarboxylase from human prostate. Activation by putrescine

Automated chromatographic analysis of human placenta polyamines

Arginase from human full-term placenta.

Multiple forms of rabbit lung indoleamine-N-methyltransferase

The molecular localization of non-tryptophan chromophores in calf lens crystallins.