Listeria monocytogenes Stimulates Mucus Exocytosis in Cultured Human Polarized Mucosecreting Intestinal Cells through Action of Listeriolysin O

When the intracellular pathogen Listeria monocytogenes infects cultured human mucosecreting polarized HT29-MTX cells apically, it induces the stimulation of mucus exocytosis without cell entry. Using a set of isogenic mutants and purified listeriolysin O (LLO), we identified the L. monocytogenes thiol-activated exotoxin LLO as the agonist of mucus secretion. We demonstrated that the LLO-induced mucus exocytosis did not result from the LLO membrane-damaging activity. We found that LLO-induced mucus exocytosis is an event requiring the binding of LLO to a brush border-associated receptor and membrane oligomerization of the exotoxin. By a pharmacological approach, we demonstrated that no regulatory system or intracellular transducing signal known to be involved in control of mucin exocytosis was activated by LLO. Based on the present data, the stimulatory action of LLO on mucin exocytosis could be accounted for either by an unknown signaling system which remains to be determined or by direct action of LLO with the membrane vesicle components involved in the intracellular vesicular transport of mucins.     

Impairment in workers with isocyanate-induced occupational asthma and removed from exposure in the province of Québec between 1985 and 2002

OBJECTIVE: The objective of this project was to assess both the outcome for patients diagnosed with proven isocyanate-induced occupational asthma (IIOA) by specific inhalation challenge (SIC) and the functional impairment, 2 years after cessation of exposure to isocyanates, using the compensation insurance scale proposed in the province of Quebec. METHODS: We used a retrospective cohort of 233 patients diagnosed in the province of Quebec between 1985 and 2002 and randomly chose 105 of those patients. We kept 89 subjects with complete data at T0 (the time of diagnosis) and 79 were reevaluated at T2, approximately 2 years after their removal from exposure, for final impairment-disability assessment. At each evaluation (T0 and T2), a clinical examination and lung function tests, including spirometry and methacholine challenge, were performed. RESULTS: At T2, 79 of 89 patients were reassessed (89%). The remaining patients were lost to follow up (8) or too unstable to be reassessed for final impairment-disability settlement (2). No statistical difference was observed for spirometry data and antiasthmatic medication use between T0 and T2 (P = 0.11). At T2, 73% of patients were still using short-acting beta2 agonists and 39% inhaled glucocorticoids. A forced expiratory volume in 1 second variation of +/-10% from T0 to T2 occurred in 31 subjects (40%). Forced expiratory volume in 1 second worsened in 14 (18%), remained significantly unchanged in 51 (64%), and improved in 14 (18%). Nonspecific bronchial hyperresponsiveness (BHR) improved in significantly in 19 (24%); the others remained unchanged. Both were not associated with smoking status (P > 0.05). Nonspecific BHR was normalized in nine of 79 (11%) patients. Clinical remission occurred in only four (5%) subjects. The mean impairment-disability score was 21% +/- 13% at 2 years according to the scale used by the Workers' Compensation Board. CONCLUSIONS: These results show the generally poor medical outcome of IIOA and suggest the importance of early detection and withdrawal of the workers from exposure to isocyanates. They also emphasize the need for medical surveillance program and adequate treatment of patients with IIOA.