Control the epithelial barrier: A pivotal first line of defense (Part 2)
Juxtaposing murine in vivo and in vitro epithelial cell culture studies, Scott et al assessed if, and then how, infection with the protozoan parasite, Giardia spp, might affect epithelial permeability. Earlier work by this group had shown that the barrier function of human nontransformed small bowel-derived epithelial cell (SCBN) monolayers was perturbed by exposure to G lamblia , a parasite that causes malabsorption and diarrhea. In the present study they demonstrated that mice infected with 2×105 live G muris trophozoites display increased small intestinal (but not gastric or colonic) permeability, as assessed by nonabsorbable sugars. In addition, this effect was T cell-independent (ie, it also occurred in athymic mice that lack thymus-educated T cells), implying a direct effect of the parasite on the epithelium.
Adopting a cell culture approach, they subsequently showed that SCBN cells cultured with G lamblia displayed an increase in myosin light chain kinase (MLCK) phosphorylation, a concomitant increase in epithelial permeability (as least to markers the size of 3000 Da fluorescein isothiocyanate-dextran (FITC), which predominantly cross the epithelial via paracellular pathways) and altered distribution of the filamentous (F)-actin cytoskeleton and tight-junc-tion associated protein, zona occludens 1 (ZO-1). These events were all inhibited by an inhibitor of MLCK phosphorylation, ML-9 (Sigma Chemical Co, USA). These in vitro data provide a mechanism by which Giardia spp infection could directly cause increased epithelial permeability, and support the postulate that arose from studies using T cell-deficient mice that the in vivo increase in permeability could be due to direct effects of the parasite on the enterocyte. Very cheap drugs at your disposal – buy alesse to get best deals at best pharmacy.