RAGE and ICAM-1 differentially control leukocyte recruitment during acute inflammation in a stimulus-dependent manner

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 o...

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Published in:	BMC immunology Vol. 12; no. 1; p. 56
Main Authors:	Frommhold, David, Kamphues, Anna, Dannenberg, Susanne, Buschmann, Kirsten, Zablotskaya, Victoria, Tschada, Raphaela, Lange-Sperandio, Baerbel, Nawroth, Peter P, Poeschl, Johannes, Bierhaus, Angelika, Sperandio, Markus
Format:	Journal Article
Language:	English
Published:	England BioMed Central Ltd 04-10-2011 BioMed Central BMC
Subjects:	Animals Cell Adhesion - genetics Cell Adhesion - immunology Cell adhesion molecules Cell receptors Cells, Cultured Chemokine CXCL1 - metabolism Chemokines Cloning Colleges & universities Flow cytometry Inflammation Intercellular Adhesion Molecule-1 - genetics Intercellular Adhesion Molecule-1 - immunology Intercellular Adhesion Molecule-1 - metabolism Leukocytes Leukocytes - immunology Leukocytes - metabolism Leukocytes - pathology Ligands Lymphocyte Function-Associated Antigen-1 - immunology Lymphocyte Function-Associated Antigen-1 - metabolism Macrophage-1 Antigen - immunology Macrophage-1 Antigen - metabolism Mice Mice, Inbred C57BL Mice, Knockout Muscles - pathology N-Formylmethionine Leucyl-Phenylalanine - metabolism Physiological aspects Protein Binding - genetics Protein Binding - immunology Receptor for Advanced Glycation End Products Receptors, Immunologic - genetics Receptors, Immunologic - metabolism Recruitment Tumor Necrosis Factor-alpha - immunology Tumor Necrosis Factor-alpha - metabolism Venules - metabolism Venules - pathology
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Summary:	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. 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. Our results demonstrate that RAGE and ICAM-1 differentially regulate leukocyte adhesion in vivo in a stimulus-dependent manner.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1471-2172 1471-2172
DOI:	10.1186/1471-2172-12-56