Schistosoma mansoni activates host microvascular endothelial cells to acquire an anti-inflammatory phenotype
In: ISSN: 0019-9567, 1999
academicJournal
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International audience ; 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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Schistosoma mansoni activates host microvascular endothelial cells to acquire an anti-inflammatory phenotype
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Autor/in / Beteiligte Person: | Trottein, François ; Descamps, Laurence ; Nutten, Sophie ; Dehouck, Marie-Pierre ; Angeli, Véronique ; Capron, André ; Cecchelli, Roméo ; Capron, Monique ; Institut Pasteur de Lille ; Réseau International des Instituts Pasteur (RIIP) ; Département d'Athérosclérose, INSERM U325 ; Institut National de la Santé et de la Recherche Médicale (INSERM) ; This work was supported by the Ministry of Research of France (grant ACC-SV6), INSERM, and the Pasteur Institute of Lille. F.T. is a member of the CNRS. ; We thank G. L. Nicolson (Institute for Molecular Medicine, Irvine, Calif.) for the generous gift of the MLE cell line. A. Wilson and P. Coulson (York University, York, United Kingdom) are acknowledged for stimulating discussion and for advice on the surgical transfer of schistosomula to naive mice. A. Verin (Johns Hopkins University, Baltimore, Md.) is acknowledged for advice on the determination of MLCK phosphorylation. |
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Zeitschrift: | ISSN: 0019-9567, 1999 |
Veröffentlichung: | HAL CCSD ; American Society for Microbiology, 1999 |
Medientyp: | academicJournal |
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