Mode of action of a potentially important excretory–secretory product fromGiardia lambliain mice enterocytes

Abstract

Giardia, a common enteric protozoan parasite is a well-recognized cause of diarrhoeal illness. The detailed mechanism of diarrhoea due to this infection is not well understood. A 58 kDa enterotoxin (ESP) was purified from the excretory-secretory product of the parasite. The present study was designed to investigate the mode of action of this enterotoxin of G. lamblia in mice enterocytes. An increase in cyclic adenosine monophosphate level, as well as intracellular Ca2+ concentration, was observed in the ESP-triggered enterocytes. The levels of phospholipase Cgamma1 and inositol triphosphate were found to be upregulated. The activity of protein kinase C (PKC) in the enterocytes was also enhanced following stimulation with the ESP. An increase in the level of reactive oxygen species in ESP-stimulated cells correlated well with the decline in the activity of antioxidant enzymes (superoxide dismutase and catalase). The significantly high levels of nitrite and citrulline indicated the generation of reactive nitrogen intermediates in the ESP-triggered enterocytes. Thus, ESP could induce cross-talk among the different signal transduction pathways in the enterocytes, which could together bring about a common secretory response.