Effects of alpha-adrenergic agonists on Toxoplasma gondii replication in human umbilical vein endothelial cells.
We investigated the effects of alpha-adrenergic on the capacity of Toxoplasma gondii to invade and proliferate in cultured human umbilical vein endothelial cells. Pretreatment of human umbilical vein endothelial cells (HUVEC) with alpha 2-adrenergic led to a high degree of intracellular killing of T. gondii in these cells. Moreover alpha 2-adrenergics activated HUVEC, induced a marked and dose-dependent toxoplasmastatic activity, whereas a pretreatment of HUVEC with alpha 1-adrenergics had no antiparasitic effects. These data suggested that antitoxoplasmal effects could involve alpha 2-adrenoreceptors. This hypothesis is supported by the abolishment of the antitoxoplasma capacities by yohimbine (an alpha 2 adreno-receptor blocker) but not by prazosin (which binds alpha 1-adrenergic receptors). Because it has been reported recently that reactive nitrogen intermediates (RNI) are essential for the inhibition of T. gondii in macrophages, we investigated whether these molecules are also involved in the alpha 2-adrenergic- dependent induction of toxoplasmastatic activity. We observed, from the incubation of HUVEC with analogs of arginine (e.g. NG-monomethyl-L-arginine) or arginase that deplete arginine, that a good correlation was found between toxoplasmastatic activity and release of NO2- during the activation phase before infection with T. gondii. No correlation was found between NO2-production during the whole infection phase of the HUVEC and toxoplasmastatic activity. These results raise the interesting possibility that alpha 2 and beta-adrenergics agonists, which naturally occur in body fluids, may regulate the transplacental transmission of T. gondii from mother to foetus.
Benedetto
N
N
Institute of Microbiology, Second University of the Studies of Naples, Italy.
Folgore
A
A
Ferrara
C
C
Molitierno
M
M
Galdiero
F
F
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000382:microbiology*; D006143:Guanabenz / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008729:Methoxamine / Q000494:pharmacology; D009585:Nitrogen Dioxide / Q000032:analysis; D014122:Toxoplasma / Q000737:chemistry / Q000502:physiology*; D014471:Umbilical Veins / Q000166:cytology*; D015016:Yohimbine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; C053113:4-iodoclonidine; D015016:Yohimbine; D006143:Guanabenz; D008729:Methoxamine; D003000:Clonidine; D009585:Nitrogen Dioxide