EFFECTS OF ALPHA-ADRENERGIC AGONISTS ON TOXOPLASMA-GONDII REPLICATIONIN HUMAN UMBILICAL VEIN ENDOTHELIAL-CELLS

We investigated the effects of alpha-adrenergic on the capacity of Tox oplasma gondii to invade and proliferate in cultured human umbilical v ein endothelial cells. Pretreatment of human umbilical vein endothelia l cells (HUVEC) with alpha(2)-adrenergic led to a high degree of intra cellular killing of T. gondii in these cells, Moreover alpha(2)-adrene rgics activated HUVEC, induced a marked and dose-dependent toxoplasmas tatic activity, whereas a pretreatment of HUVEC with alpha(1)-adrenerg ics had no antiparasitic effects. These data suggested that antitoxopl asmal effects could involve alpha(2)-adrenoreceptors. This hypothesis is supported by the abolishment of the antitoxoplasma capacities by yo himbine (an alpha(2) adreno-receptor blocker) but not by prazosin (whi ch binds al-adrenergic receptors). Because it has been reported recent ly that reactive nitrogen intermediates (RNI) are essential for the in hibition of T. gondii in macrophages, we investigated whether these mo lecules are also involved in the alpha(2)-adrenergic- dependent induct ion of toxoplasmastatic activity. We observed, from the incubation of HUVEC with analogs of arginine (e.g. N-G- monomethyl-L-arginine) or ar ginase that deplete arginine, that a good correlation was found betwee n toxoplasmastatic activity and release of NO2- during the activation phase before infection with T. gondii. No correlation was found betwee n NO2- production during the whole infection phase of HUVEC and toxopl asmastatic activity. These results raise the interesting possibility t hat alpha(2) and beta-adrenergics agonists, which naturally occur in b ody fluids, may regulate the transplacental transmission of T. gondii from mother to foetus.