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Schistosoma mansoni activates host microvascular endothelial cells to acquire an anti-inflammatory phenotype

François Trottein 1 Laurence Descamps 2, 1 Sophie Nutten 1 Marie-Pierre Dehouck 2, 1 Véronique Angeli 1 André Capron 1 Roméo Cecchelli 2, 1 Monique Capron 1 
2 Département d'Athérosclérose, INSERM U325
INSERM - Institut National de la Santé et de la Recherche Médicale : U325
Abstract : Since endothelial cells (ECs) play a key role in immune defense mechanisms and in immunopathology, we investigated whether the intravascular helminth parasite Schistosoma mansoni could interact with and activate resting ECs in vitro. Microscopic analysis revealed that the lung-stage schistosomula specifically attached to microvascular ECs. This adherence was associated to active cellular processes involving actin filament formation. Since variation of permeability of cultured capillary brain ECs is a good marker for endothelial activation, the transendothelial passage of a low-molecular-weight molecule (inulin) on monolayers of bovine brain capillary ECs (BBCEC) was measured in response to parasites. Schistosomula induced a dramatic decrease in transendothelial permeability, a characteristic marker for the generation of an anti-inflammatory phenotype to ECs. This paracellular barrier enhancing effect on endothelial monolayers was due to a soluble substance(s) (below 1 kDa in size) secreted from S. mansoni schistosomula and not by mechanisms associated to adherence between parasites and ECs. The reinforcement of the endothelial barrier function was accompanied by an elevation of intracellular concentration of cyclic AMP (cAMP). The use of specific kinase inhibitors confirms that schistosomula activate ECs through a cAMP/protein kinase A pathway that leads to an increased phosphorylation of the myosin light-chain kinase. These combined findings suggest that the secretory/excretory products from schistosomula possess anti-inflammatory factor(s) that signal host microvascular endothelium. The immunological consequences of such activation are discussed.
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Submitted on : Wednesday, November 3, 2010 - 4:44:40 PM
Last modification on : Tuesday, November 3, 2020 - 3:30:06 PM

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François Trottein, Laurence Descamps, Sophie Nutten, Marie-Pierre Dehouck, Véronique Angeli, et al.. Schistosoma mansoni activates host microvascular endothelial cells to acquire an anti-inflammatory phenotype. Infection and Immunity, 1999, 67 (7), pp.3403-3409. ⟨hal-00531758⟩



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