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

BMC Immunology

Research Article

Peter P Nawroth¹  Angelika Bierhaus¹  Victoria Zablotskaya²  Raphaela Tschada²  Susanne Dannenberg²  Kirsten Buschmann²  David Frommhold²  Anna Kamphues²  Johannes Poeschl²  Baerbel Lange-Sperandio³  Markus Sperandio⁴ 

[1] Department of Medicine I and Clinical Chemistry, University of Heidelberg, 69120, Heidelberg, Germany;Department of Neonatology, University of Heidelberg, 69120, Heidelberg, Germany;Dr. von Haunersches Kinderspital Ludwig-Maximilians-University, 81377, München, Germany;Walter Brendel Center of Experimental Medicine, Ludwig-Maximilians-University, 81377, München, Germany;

关键词: Wild Type Mouse;    Leukocyte Adhesion;    Intravital Microscopy;    Postcapillary Venule;    Cremaster Muscle;   

DOI  :  10.1186/1471-2172-12-56

 received in 2011-05-06, accepted in 2011-10-04,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundThe 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.ResultsWe 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.ConclusionOur results demonstrate that RAGE and ICAM-1 differentially regulate leukocyte adhesion in vivo in a stimulus-dependent manner.

【 授权许可】

CC BY   
© Frommhold et al; licensee BioMed Central Ltd. 2011