Journal article
Binding of CD40L to Mac-1's i-domain involves the EQLKKSKTL motif and mediates leukocyte recruitment and atherosclerosis-but does not affect immunity and thrombosis in mice
D Wolf, JD Hohmann, A Wiedemann, K Bledzka, H Blankenbach, T Marchini, K Gutte, K Zeschky, N Bassler, N Hoppe, AO Rodriguez, N Herr, I Hilgendorf, P Stachon, F Willecke, D Duerschmied, C Von Zur Muhlen, DA Soloviev, L Zhang, C Bode Show all
Circulation Research | LIPPINCOTT WILLIAMS & WILKINS | Published : 2011
Abstract
Rationale: CD40L figures prominently in chronic inflammatory diseases such as atherosclerosis. However, since CD40L potently regulates immune function and hemostasis by interaction with CD40 receptor and the platelet integrin GPIIb/IIIa, its global inhibition compromises host defense and generated thromboembolic complications in clinical trials. We recently reported that CD40L mediates atherogenesis independently of CD40 and proposed Mac-1 as an alternate receptor. Objective: Here, we molecularly characterized the CD40L-Mac-1 interaction and tested whether its selective inhibition by a small peptide modulates inflammation and atherogenesis in vivo. Methods and Results: CD40L concentration-de..
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Awarded by National Heart, Lung, and Blood Institute
Funding Acknowledgements
We thank Daniel Topcic from the Baker IDI Heart and Diabetes Institute Melbourne for advice on recombinant protein production, Patrick Stoll and Rene Schmidt from the University of Freiburg for their support with intravital microscopy. We thank Andreas Straub from the University of Tubingen for his assistance in intravital microscopy and for proofreading of the manuscript, as well as Sandra Ernst and Christian Munkel for technical support and Sara Karwacki for editorial assistance.This work was supported by research grants from the Deutsche Forschungsgemeinschaft (DFG ZI743/3-1 and 3-2) and from the Else-Kroner-Fresenius Stiftung (EKFS P30/10//A43/10) to Dr Zirlik, grant HL 34636 from the National Institutes of Health to Dr Libby, and grants from the National Health and Medical Research Council of Australia to Dr Peter. Dr Peter is a Future Fellow of the Australian Research Council. Dr Wolf was funded by a fellowship of the Bayer Science and Education Foundation.