Matches in SemOpenAlex for { <https://semopenalex.org/work/W4254156634> ?p ?o ?g. }
Showing items 1 to 70 of
70
with 100 items per page.
- W4254156634 endingPage "3" @default.
- W4254156634 startingPage "3" @default.
- W4254156634 abstract "The thrombogenic effect of β2-glycoprotein I (β2GPI)-dependent anti-phospholipid antibodies (aPL) in animal models was found to be LPS dependent. Since β2GPI behaves as LPS scavenger, LPS/β2GPI complex was suggested to account for in vitro cell activation through LPS/TLR4 involvement being LPS the actual bridge ligand between β2GPI and TLR4 at least in monocytes/macrophages. However, no definite information is available on the interaction among β2GPI, LPS and endothelial TLR4 in spite of the main role of endothelial cells (EC) in clotting. To analyse at the endothelial level the need of LPS, we investigated the in vitro interaction of β2GPI with endothelial TLR4 and we assessed the role of LPS in such an interaction.To do this, we evaluated the direct binding and internalization of β2GPI by confocal microscopy in living TLR4-MD2 transfected CHO cells (CHO/TLR4-MD2) and β2GPI binding to CHO/TLR4-MD2 cells and human umbilical cord vein EC (HUVEC) by flow cytometry and cell-ELISA using anti-β2GPI monoclonal antibodies in the absence or presence of various concentrations of exogenous LPS. To further investigate the role of TLR4, we performed anti-β2GPI antibody binding and adhesion molecule up-regulation in TLR4-silenced HUVEC.Confocal microscopy studies show that β2GPI does interact with TLR4 at the cell membrane and is internalized in cytoplasmic granules in CHO/TLR4-MD2 cells. β2GPI binding to CHO/TLR4-MD2 cells and HUVEC is also confirmed by flow cytometry and cell-ELISA, respectively. The interaction between β2GPI and TLR4 is confirmed by the reduction of anti-β2GPI antibody binding and by the up-regulation of E-selectin or ICAM-1 by TLR4 silencing in HUVEC. β2GPI binding is not affected by LPS at concentrations comparable to those found in both β2GPI and antibody preparations. Only higher amount of LPS that can activate EC and up-regulate TLR4 expression are found to increase the binding.Our findings demonstrate that β2GPI interacts directly with TLR4 expressed on EC, and that such interaction may contribute to β2GPI-dependent aPL-mediated EC activation. At variance of monocytic cells, we also showed a threshold effect for the action of LPS, that is able to enhance anti-β2GPI antibody EC binding only at cell activating concentrations, shown to increase TLR4 expression. This in vitro model may explain why LPS behaves as a second hit increasing the expression of β2GPI in vascular tissues and triggering aPL-mediated thrombosis in experimental animals." @default.
- W4254156634 created "2022-05-12" @default.
- W4254156634 creator A5075174977 @default.
- W4254156634 date "2003-01-01" @default.
- W4254156634 modified "2023-09-26" @default.
- W4254156634 title "Preface" @default.
- W4254156634 doi "https://doi.org/10.1078/0171-2985-00206" @default.
- W4254156634 hasPublicationYear "2003" @default.
- W4254156634 type Work @default.
- W4254156634 citedByCount "0" @default.
- W4254156634 crossrefType "journal-article" @default.
- W4254156634 hasAuthorship W4254156634A5075174977 @default.
- W4254156634 hasConcept C123012128 @default.
- W4254156634 hasConcept C136449434 @default.
- W4254156634 hasConcept C139770010 @default.
- W4254156634 hasConcept C1491633281 @default.
- W4254156634 hasConcept C153911025 @default.
- W4254156634 hasConcept C170493617 @default.
- W4254156634 hasConcept C185592680 @default.
- W4254156634 hasConcept C202751555 @default.
- W4254156634 hasConcept C2776070231 @default.
- W4254156634 hasConcept C2776709828 @default.
- W4254156634 hasConcept C2777411675 @default.
- W4254156634 hasConcept C2779178360 @default.
- W4254156634 hasConcept C54009773 @default.
- W4254156634 hasConcept C54355233 @default.
- W4254156634 hasConcept C553184892 @default.
- W4254156634 hasConcept C55493867 @default.
- W4254156634 hasConcept C81885089 @default.
- W4254156634 hasConcept C86803240 @default.
- W4254156634 hasConcept C95444343 @default.
- W4254156634 hasConceptScore W4254156634C123012128 @default.
- W4254156634 hasConceptScore W4254156634C136449434 @default.
- W4254156634 hasConceptScore W4254156634C139770010 @default.
- W4254156634 hasConceptScore W4254156634C1491633281 @default.
- W4254156634 hasConceptScore W4254156634C153911025 @default.
- W4254156634 hasConceptScore W4254156634C170493617 @default.
- W4254156634 hasConceptScore W4254156634C185592680 @default.
- W4254156634 hasConceptScore W4254156634C202751555 @default.
- W4254156634 hasConceptScore W4254156634C2776070231 @default.
- W4254156634 hasConceptScore W4254156634C2776709828 @default.
- W4254156634 hasConceptScore W4254156634C2777411675 @default.
- W4254156634 hasConceptScore W4254156634C2779178360 @default.
- W4254156634 hasConceptScore W4254156634C54009773 @default.
- W4254156634 hasConceptScore W4254156634C54355233 @default.
- W4254156634 hasConceptScore W4254156634C553184892 @default.
- W4254156634 hasConceptScore W4254156634C55493867 @default.
- W4254156634 hasConceptScore W4254156634C81885089 @default.
- W4254156634 hasConceptScore W4254156634C86803240 @default.
- W4254156634 hasConceptScore W4254156634C95444343 @default.
- W4254156634 hasIssue "1" @default.
- W4254156634 hasLocation W42541566341 @default.
- W4254156634 hasOpenAccess W4254156634 @default.
- W4254156634 hasPrimaryLocation W42541566341 @default.
- W4254156634 hasRelatedWork W2281208687 @default.
- W4254156634 hasRelatedWork W2350572624 @default.
- W4254156634 hasRelatedWork W2356588131 @default.
- W4254156634 hasRelatedWork W2372462472 @default.
- W4254156634 hasRelatedWork W2372746874 @default.
- W4254156634 hasRelatedWork W2387911498 @default.
- W4254156634 hasRelatedWork W2394081135 @default.
- W4254156634 hasRelatedWork W2792230831 @default.
- W4254156634 hasRelatedWork W2974669612 @default.
- W4254156634 hasRelatedWork W3092750669 @default.
- W4254156634 hasVolume "207" @default.
- W4254156634 isParatext "false" @default.
- W4254156634 isRetracted "false" @default.
- W4254156634 workType "article" @default.