Solomon, K.; Robins, R.A.; Mahida, Y.R.
April 2003
Gut;Apr2003 Supplement 1, Vol. 52, pA54
Academic Journal
Introduction: C difficile causes an intense inflammatory colitis through the actions of secreted toxins A and B. Responses of immune cells to C difficile toxins appear to be pivotal in the progression of the disease. We have investigated the effects, of toxin A on peripheral blood mononuclear cells (PBMNCs). Methods: PBMNCs and purified monocytes were exposed to 1-1000 ng/ml of purified toxin A. Cells were studied by flow cytometry (FACS), Hoechst staining and electron microscopy (EM). Results: In PMNCs, proportions of CD3 events (T cells) and CD19 events (B cells) did not change significantly in response to toxin A for up to 72 h. By contrast, CD14 events (monocytes) were lost in a dose and time dependent fashion (table). Hoechst staining of purified monocytes exposed to >10 ng/ml toxin A showed many cells with nuclear fragmentation characteristic of apoptotic cells. DNA fragmentation was confirmed by analysis of propidium iodide-stained monocytes exposed to high conc. of toxin A. EM of toxin A-exposed purified monocytes confirmed the presence of numerous apoptotic cells, but also of some cells showing features of necrotic cell death. Conclusion: 1. Within 24 h exposure to high concentrations of C difficile toxin A cell death is induced in peripheral blood monocytes but not T and B cells. 2. Toxin A-induced monocyte cell death occurs by apoptosis although in some, features of necrotic cell death were also seen. 3. Early loss of monocytes would impair host innate and adaptive immune responses to C difficile toxins.


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