Frommhold, David; Kamphues, Anna; Dannenberg, Susanne; Buschmann, Kirsten; Zablotskaya, Victoria; Tschada, Raphaela; Lange-Sperandio, Baerbel; Nawroth, Peter P.; Poeschl, Johannes; Bierhaus, Angelika; Sperandio, Markus:
RAGE and ICAM-1 differentially control leukocyte recruitment during acute inflammation in a stimulus-dependent manner.
In: BMC Immunology
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-kappa B but also due to its function as ligand for the beta(2)-integrin Mac-1. To further dissect the stimulus-dependent role of RAGE on leukocyte recruitment during inflammation, we investigated beta(2)-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-leucylphenylalanine (fMLP)-induced leukocyte adhesion in TNF-alpha-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. Conclusion: Our results demonstrate that RAGE and ICAM-1 differentially regulate leukocyte adhesion in vivo in a stimulus-dependent manner.