INVESTIGADORES
GIOVAMBATTISTA Andres
artículos
Título:
A phospholipase A2-related snake venom (from Crotalus durissus terrificus) stimulates neuroendocrine and immune functions: determination of different sites of action.
Autor/es:
CHISARI, A; SPINEDI, E; VOIROL MJ; GIOVAMBATTISTA A; GAILLARD, R
Revista:
ENDOCRINOLOGY
Editorial:
ENDOCRINE SOC
Referencias:
Año: 1998 vol. 139 p. 617 - 625
ISSN:
0013-7227
Resumen:
Immune neuroendocrine interactions are vital for the individual's
survival in certain physiopathological conditions, such as sepsis and tissular
injury. It is known that several animal venoms, such as those from different
snakes, are potent neurotoxic compounds and that their main component is a
specific phospholipase A type 2 (PLA2). It has been described recently that the
venom from Crotalus durissus terrificus [snake venom (SV), in the present
study] possesses some cytotoxic effect in different in vitro and in vivo animal
models. In the present study, we investigated whether SV and its main
component, PLA2 (obtained from the same source), are able to stimulate both
immune and neuroendocrine functions in mice, thus characterizing this type of
neurotoxic shock. For this purpose, several in vivo and in vitro designs were
used to further determine the sites of action of SV-PLA2 on the
hypothalamo-pituitary-adrenal (HPA) axis function and on the release of the
pathognomonic cytokine, tumor necrosis factor alpha (TNF alpha), of different
types of inflammatory stress. Our results indicate that SV (25 microg/animal)
and PLA2 (5 microg/animal), from the same origin, stimulate the HPA and immune
axes when administered (i.p.) to adult mice; both preparations were able to
enhance plasma glucose, ACTH, corticosterone (B), and TNF alpha plasma levels
in a time-related fashion. SV was found to activate CRH- and arginine
vasopressin-ergic functions in vivo and, in vitro, SV and PLA2 induced a
concentration-related (0.05-10 microg/ml) effect on the release of both
neuropeptides. SV also was effective in changing anterior pituitary ACTH and
adrenal B contents, also in a time-dependent fashion. Direct effects of SV and
PLA2 on anterior pituitary ACTH secretion also were found to function in a
concentration-related fashion (0.001-1 microg/ml), and the direct
corticotropin-releasing activity of PLA2 was additive to those of CRH and
arginine vasopressin; the corticotropin-releasing activity of both SV and PLA2
were partially reversed by the specific PLA2 inhibitor, manoalide. On the other
hand, neither preparation was able to directly modify spontaneous and
ACTH-stimulated adrenal B output. The stimulatory effect of SV and PLA2 on in
vivo TNF alpha release was confirmed by in vitro experiments on peripheral
mononuclear cells; in fact, both PLA2 (0.001-1 microg/ml) and SV (0.1-10
microg/ml), as well as concavalin A (1-100 microg/ml), were able to stimulate
TNF alpha output in the incubation medium. Our results clearly indicate that
PLA2-dependent mechanisms are responsible for several symptoms of inflammatory
stress induced during neurotoxemia. In fact, we found that this particular
PLA2-related SV is able to stimulate both HPA axis and immune functions during
the acute phase response of the inflammatory processes.