Tetanus toxin impairs accessory and secretory functions in interferon-gamma-treated murine macrophages

Tetanus neurotoxin (TT), a product of microbial origin, acts as a zinc endo peptidase on vesicle-associated membrane proteins (VAMP). We have demonstra ted that TT displays inhibitory effects on secretory and accessory function s in the murine macrophage (M phi) cell line GG2EE, Nitric oxide (NO) secre tion was decreased when interferon (IFN)-gamma-pretreated GG2EE M phi s wer e coincubated with a fungal costimulus (SMP200) and TT, When heat-inactivat ed TT was used this effect was not evident, The TT-mediated phenomenon was dose-dependent and specific since, under the same experimental conditions, it did not affect interleukin-6 or tumor necrosis factor-alpha secretion. F urthermore, IFN-gamma-induced major histocompatibility complex class II mol ecule expression and GG2EE accessory function, assessed by SMP200-stimulate d lymphoproliferation, were also inhibited by TT, Such inhibition was incom plete, in line with our previous results showing that TT partially cleaves VAMP proteins in murine M phi. (C) 1999 Academic Press.