title: RAGE and ICAM-1 differentially control leukocyte recruitment during acute inflammation in a stimulus-dependent manner.
abstract: BACKGROUND
  The receptor for advanced glycation endproducts, RAGE, is involved in the pathogenesis of many inflammatory conditions, which is mostly related to its strong activation of NF-κB but also due to its function as ligand for the β2-integrin Mac-1. To further dissect the stimulus-dependent role of RAGE on leukocyte recruitment during inflammation, we investigated β2-integrin-dependent leukocyte adhesion in RAGE-/- and Icam1-/- mice in different cremaster muscle models of inflammation using intravital microscopy.
  
  
  RESULTS
  We demonstrate that RAGE, but not ICAM-1 substantially contributes to N-formyl-methionyl-leucyl-phenylalanine (fMLP)-induced leukocyte adhesion in TNF-α-pretreated cremaster muscle venules in a Mac-1-dependent manner. In contrast, fMLP-stimulated leukocyte adhesion in unstimulated cremaster muscle venules is independent of RAGE, but dependent on ICAM-1 and its interaction with LFA-1. Furthermore, chemokine CXCL1-stimulated leukocyte adhesion in surgically prepared cremaster muscle venules was independent of RAGE but strongly dependent on ICAM-1 and LFA-1 suggesting a differential and stimulus-dependent regulation of leukocyte adhesion during inflammation in vivo.
  
  
  CONCLUSIONS
  Our results demonstrate that RAGE and ICAM-1 differentially regulate leukocyte adhesion in vivo in a stimulus-dependent manner.
authors.affiliation: Department of Neonatology, University of Heidelberg,20 Heidelberg, Germany. David_Frommhold@med.uni-heidelberg.de
authors.forename: David
authors.initials: D
authors.lastname: Frommhold
authors.forename: Anna
authors.initials: A
authors.lastname: Kamphues
authors.forename: Susanne
authors.initials: S
authors.lastname: Dannenberg
authors.forename: Kirsten
authors.initials: K
authors.lastname: Buschmann
authors.forename: Victoria
authors.initials: V
authors.lastname: Zablotskaya
authors.forename: Raphaela
authors.initials: R
authors.lastname: Tschada
authors.forename: Baerbel
authors.initials: B
authors.lastname: Lange-Sperandio
authors.forename: Peter P
authors.initials: PP
authors.lastname: Nawroth
authors.forename: Johannes
authors.initials: J
authors.lastname: Poeschl
authors.forename: Angelika
authors.initials: A
authors.lastname: Bierhaus
authors.forename: Markus
authors.initials: M
authors.lastname: Sperandio
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D054360:Chemokine CXCL1 / Q000378:metabolism; D007249:Inflammation; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology / Q000378:metabolism*; D016177:Macrophage-1 Antigen / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009132:Muscles / Q000473:pathology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000378:metabolism; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism; D014699:Venules / Q000378:metabolism* / Q000473:pathology
chemical_list: D054360:Chemokine CXCL1; D016169:Lymphocyte Function-Associated Antigen-1; D016177:Macrophage-1 Antigen; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D009240:N-Formylmethionine Leucyl-Phenylalanine