ABSTRACT
The present study documents that in Bioniphalaria alexandrina coordinated responses to Schistosoma mansoni infection are modulated by receptor-mediated opioid signals. Rather comprehensive tests in susceptible and resistant snails have demonstrated: I- the presence of an endogenaus opioids in the snail hemolymph (in particular, Leu-enkephalin-like material). II- in vitro treatment of snail hemocytes with synthetic Leu-enkephalin analogue (DADLE) resulted in the modulation of cellular adherence, and phagocytic activity. III- the addition of Naloxone, either alone or in combination whith DADLE, generally reduced hemocyte activity indicating opioid-receptor-mediated mechanism. V- the presence of DADLE or Naloxone modulated the level of IL-2-, TNF-gamma- and FNF-alpha-like molecules in S. mansoni resistant and susceptible snails. Specifically, DADLE and DADLE in combination with Naloxone generally were found to be capable of modulating resistant snail hemocytes at concentrations of 10(-6) and 10(-8) M. Similar actions after incubation with the same concentrations were not detected in the susceptible snails. These observations demonstrate the existence of a complete opioid system in B. alexandrina, associated with susceptibility and resistance to S. mansoni infection, the results suggest the role of such opioid system in molecular signaling within the host and in host-parasite interactions.
Subject(s)
Biomphalaria/parasitology , Enkephalin, Leucine-2-Alanine/pharmacology , Enkephalin, Leucine/physiology , Naloxone/pharmacology , Narcotic Antagonists/pharmacology , Schistosoma mansoni/immunology , Animals , Biomphalaria/immunology , Blood Cell Count/veterinary , Disease Susceptibility/veterinary , Enkephalin, Leucine/drug effects , Enkephalin, Leucine/metabolism , Enkephalin, Leucine-2-Alanine/physiology , Hemocytes/drug effects , Hemocytes/immunology , Hemocytes/parasitology , Host-Parasite Interactions , Phagocytosis/drug effects , Receptors, Opioid/drug effects , Receptors, Opioid/metabolismABSTRACT
DADL, a delta-receptor selective enkephalin analogue, was prepared with the technique of solid-phase peptide synthesis. It was found to stimulate directly the proliferation of mouse splenic lymphocytes dose-dependently. However, synergistic effect of DADL at different concentrations with ConA and LPS were not found. In addition, TNF-alpha production was increased by ip DADL (1.0 mg.kg-1 x 6 d) in mice and the production of LPS-induced TNF-alpha in mouse peritoneal macrophages was enhanced after DADL was added in vitro. These results suggest that DADL, like enkephalins, exerts some immunoregulatory activities.
