RAGE and ICAM-1 differentially control leukocyte recruitment during acute inflammation in a stimulus-dependent manner
1 Department of Neonatology, University of Heidelberg, 69120 Heidelberg, Germany
2 Department of Medicine I and Clinical Chemistry, University of Heidelberg, 69120 Heidelberg, Germany
3 Dr. von Haunersches Kinderspital Ludwig-Maximilians-University, 81377 München, Germany
4 Walter Brendel Center of Experimental Medicine, Ludwig-Maximilians-University, 81377 München, Germany
BMC Immunology 2011, 12:56 doi:10.1186/1471-2172-12-56Published: 4 October 2011
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.