title: Heterogenic endothelial responses to inflammation: role for differential N-glycosylation and vascular bed of origin.
abstract: BACKGROUND
  Endothelial cell responses during inflammation are heterogeneous and key for selectivity in how leukocytes hone in on specific sites and why vascular diseases are highly bed specific. However, mechanisms for this specificity remain unclear.
  
  
  RESULTS
  Here, we exposed human endothelial cells isolated from 5 systemic arterial beds from 1 donor (to overcome donor-to-donor genetic/epigenetic differences), the umbilical vein, and pulmonary microvasculature to TNF-α, LPS, and IL-1β and assessed acute (ERK1/2 and p65) and chronic (ICAM-1, VCAM-1 total and surface expression) signaling responses and assessed changes in surface N-glycans and monocyte adhesion. Significant diversity in responses was evident by disparate changes in ERK1/2 and p65 NF-κB phosphorylation, which varied up to 5-fold between different cells and in temporal and magnitude differences in ICAM-1 and VCAM-1 expression (maximal VCAM-1 induction typically being observed by 4 hours, whereas ICAM-1 expression was increased further at 24 hours relative to 4 hours). N-glycan profiles both basally and with stimulation were also bed specific, with hypoglycosylated N-glycans correlating with increased THP-1 monocyte adhesion. Differences in surface N-glycan expression tracked with dynamic up- or downregulation of α-mannosidase activity during inflammation.
  
  
  CONCLUSIONS
  These results demonstrate a critical role for the vascular bed of origin in controlling endothelial responses and function to inflammatory stimuli and suggest that bed-specific expression of N-linked sugars may provide a signature for select leukocyte recruitment.
authors.affiliation: Department of Pathology and Comprehensive Cardiovascular Center, University of Alabama at Birmingham, Birmingham, AL.
authors.forename: David W
authors.initials: DW
authors.lastname: Scott
authors.forename: Matthew O
authors.initials: MO
authors.lastname: Vallejo
authors.forename: Rakesh P
authors.initials: RP
authors.lastname: Patel
mesh_terms: D001011:Aorta / Q000276:immunology / Q000378:metabolism; D016122:Brachiocephalic Trunk / Q000276:immunology / Q000378:metabolism; D002339:Carotid Arteries / Q000276:immunology / Q000378:metabolism; D002448:Cell Adhesion; D002460:Cell Line; D002634:Chemotaxis, Leukocyte; D003331:Coronary Vessels / Q000276:immunology / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D005260:Female; D006031:Glycosylation; D061307:Human Umbilical Vein Endothelial Cells / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000098:blood supply*; D008297:Male; D055806:Microvessels / Q000276:immunology / Q000378:metabolism; D008875:Middle Aged; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D010766:Phosphorylation; D015398:Signal Transduction; D013348:Subclavian Artery / Q000276:immunology / Q000378:metabolism; D013997:Time Factors; D051996:Transcription Factor RelA / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: C573420:ICAM1 protein, human; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; C498143:RELA protein, human; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
keywords: N‐glycans; heterogeneity; mannose
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