Matches in SemOpenAlex for { <https://semopenalex.org/work/W2912651472> ?p ?o ?g. }
Showing items 1 to 78 of
78
with 100 items per page.
- W2912651472 abstract "During inflammation, such as ischemia reperfusion injury or atherosclerosis, excessive neutrophil infiltration drives pathogenesis. Yet, the relationship between neutrophil transmigration and inflammation is ill-defined. Neutrophils migrate through endothelial cells (EC) via para (between EC) and transcellular (through an EC, TCM) mechanisms. During TCM, neutrophils interact with EC via invadopodia-like structures to form a ‘pore’ into EC membrane, thus facilitating neutrophil migration through EC body. We recently reported that deficiency in Rap1b, a member of RasGTPase superfamily, enhanced neutrophil recruitment to inflamed lungs and susceptibility to endotoxin shock. Rap1b-/- neutrophils exhibit increased TCM, invadopodia-like formation and metalloproteinase (MMP) release, suggesting mode of migration may influence inflammation outcome. Here, we used Rap1b-/- neutrophils to further investigate the link between neutrophil migration and inflammation. Using mass spectrometry, we found 2-fold increase in glycolytic enzymes hexokinase1, LDHA and PGK1, in Rap1b-/- protrusions compared to WT. Immunofluorescent staining and western blotting confirmed this observation. Inhibition of LDHA with a specific inhibitor FX11, inhibited Rap1b-/- invadopodia protrusions, MMP release and TCM. We then tested effects of LDHA inhibition on neutrophil transendothelial migration in vivo. Rap1b-/- and WT neutrophils were tagged with cell tracker dyes and transferred to recipient mice, treated with FX11 or DMSO control. Ear microvasculature was stimulated with FMLP and labeled with PECAM antibody to visualize EC junctions. More Rap1b-/- cells migrated out of vessels compared to WT cells at the same vascular environment. FX11 treatment significantly abrogated this increase. This suggests that LDHA and enhanced glycolytic metabolism play critical roles during transmigration in vivo perhaps by changing neutrophil migratory behavior and inflammation outcome. Since lactate, the glycolytic byproduct, induces milieu acidification and acidity play a major role in ischemic damage to the heart, our findings may be important for our understanding of cardiovascular injury and for the development of approaches for effective treatment." @default.
- W2912651472 created "2019-02-21" @default.
- W2912651472 creator A5001578737 @default.
- W2912651472 creator A5032399596 @default.
- W2912651472 creator A5064566910 @default.
- W2912651472 creator A5073882436 @default.
- W2912651472 creator A5079495532 @default.
- W2912651472 creator A5087812279 @default.
- W2912651472 date "2017-11-14" @default.
- W2912651472 modified "2023-10-16" @default.
- W2912651472 title "Abstract 21312: Lactate Dehydrogenase A Affects Neutrophil Transcellular Extravasation by Upregulating Invadopodia Signaling" @default.
- W2912651472 doi "https://doi.org/10.1161/circ.136.suppl_1.21312" @default.
- W2912651472 hasPublicationYear "2017" @default.
- W2912651472 type Work @default.
- W2912651472 sameAs 2912651472 @default.
- W2912651472 citedByCount "0" @default.
- W2912651472 crossrefType "journal-article" @default.
- W2912651472 hasAuthorship W2912651472A5001578737 @default.
- W2912651472 hasAuthorship W2912651472A5032399596 @default.
- W2912651472 hasAuthorship W2912651472A5064566910 @default.
- W2912651472 hasAuthorship W2912651472A5073882436 @default.
- W2912651472 hasAuthorship W2912651472A5079495532 @default.
- W2912651472 hasAuthorship W2912651472A5087812279 @default.
- W2912651472 hasConcept C121608353 @default.
- W2912651472 hasConcept C126322002 @default.
- W2912651472 hasConcept C150903083 @default.
- W2912651472 hasConcept C176285220 @default.
- W2912651472 hasConcept C181199279 @default.
- W2912651472 hasConcept C200786668 @default.
- W2912651472 hasConcept C20251656 @default.
- W2912651472 hasConcept C203014093 @default.
- W2912651472 hasConcept C207001950 @default.
- W2912651472 hasConcept C2776914184 @default.
- W2912651472 hasConcept C2777318727 @default.
- W2912651472 hasConcept C2910680157 @default.
- W2912651472 hasConcept C55493867 @default.
- W2912651472 hasConcept C62231903 @default.
- W2912651472 hasConcept C71924100 @default.
- W2912651472 hasConcept C86803240 @default.
- W2912651472 hasConcept C95444343 @default.
- W2912651472 hasConcept C96232424 @default.
- W2912651472 hasConceptScore W2912651472C121608353 @default.
- W2912651472 hasConceptScore W2912651472C126322002 @default.
- W2912651472 hasConceptScore W2912651472C150903083 @default.
- W2912651472 hasConceptScore W2912651472C176285220 @default.
- W2912651472 hasConceptScore W2912651472C181199279 @default.
- W2912651472 hasConceptScore W2912651472C200786668 @default.
- W2912651472 hasConceptScore W2912651472C20251656 @default.
- W2912651472 hasConceptScore W2912651472C203014093 @default.
- W2912651472 hasConceptScore W2912651472C207001950 @default.
- W2912651472 hasConceptScore W2912651472C2776914184 @default.
- W2912651472 hasConceptScore W2912651472C2777318727 @default.
- W2912651472 hasConceptScore W2912651472C2910680157 @default.
- W2912651472 hasConceptScore W2912651472C55493867 @default.
- W2912651472 hasConceptScore W2912651472C62231903 @default.
- W2912651472 hasConceptScore W2912651472C71924100 @default.
- W2912651472 hasConceptScore W2912651472C86803240 @default.
- W2912651472 hasConceptScore W2912651472C95444343 @default.
- W2912651472 hasConceptScore W2912651472C96232424 @default.
- W2912651472 hasIssue "suppl_1" @default.
- W2912651472 hasLocation W29126514721 @default.
- W2912651472 hasOpenAccess W2912651472 @default.
- W2912651472 hasPrimaryLocation W29126514721 @default.
- W2912651472 hasRelatedWork W2411177191 @default.
- W2912651472 hasRelatedWork W2727015719 @default.
- W2912651472 hasRelatedWork W2887157979 @default.
- W2912651472 hasRelatedWork W2887879798 @default.
- W2912651472 hasRelatedWork W2888945681 @default.
- W2912651472 hasRelatedWork W2924369475 @default.
- W2912651472 hasRelatedWork W3177991739 @default.
- W2912651472 hasRelatedWork W4307331301 @default.
- W2912651472 hasRelatedWork W4319812687 @default.
- W2912651472 hasRelatedWork W2608923016 @default.
- W2912651472 hasVolume "136" @default.
- W2912651472 isParatext "false" @default.
- W2912651472 isRetracted "false" @default.
- W2912651472 magId "2912651472" @default.
- W2912651472 workType "article" @default.