Sue Chandraratne1, Marie-Luise von Bruehl1, Judith-Irina Pagel1, Konstantin Stark1, Eike Kleinert1, Ildiko Konrad1, Said Farschtschi1, Raffaele Coletti1, Florian Gärtner1, Omari Chillo1, Kyle R Legate1, Michael Lorenz1, Simon Rutkowski1, Amelia Caballero-Martinez1, Richard Starke1, Anca Tirniceriu1, Laurenz Pauleikhoff1, Silvia Fischer1, Gerald Assmann1, Josef Mueller-Hoecker1, Jerry Ware1, Bernhard Nieswandt1, Wolfgang Schaper1, Christian Schulz1, Elisabeth Deindl1, Steffen Massberg2. 1. From the Medizinische Klinik und Poliklinik I, Department of Cardiology (S.C., M.-L.v.B., K.S., I.K., S.F., R.C., F.G., K.R.L., M.L., A.T., C.S., S.M.), Walter-Brendel-Centre of Experimental Medicine (S.C., M.-L.v.B., J.-I.P., K.S., E.K., I.K., S.F., R.C., F.G., O.C., K.R.L., M.L., S.R., A.C.-M., A.T., L.P., C.S., E.D., S.M.), Department of Anaesthesiology (J.-I.P.), Department of Applied Physics (K.R.L.), and Institute of Pathology (G.A., J.M.-H.), Ludwig-Maximilians-Universität, Munich, Germany; DZHK (German Centre for Cardiovascular Research), Berlin, Germany (S.C., M.-L.v.B., K.S., I.K., S.F., R.C., F.G., K.R.L., M.L., A.T., C.S., S.M); Department of Biochemistry, Medical School, Justus-Liebig-University, Giessen, Germany (S.F.); Vascular Sciences, National Heart and Lung Institute, Faculty of Medicine, Hammersmith Campus, Imperial College London, South Kensington Campus, London, United Kingdom (R.S.); Department of Physiology and Biophysics, University of Arkansas for Medical Science, Little Rock (J.W.); Rudolf Virchow Center and DFG Research Center for Experimental Biomedicine, Universität Würzburg, Würzburg, Germany (B.N.); and Max Planck Institute for Heart and Lung Research, Giessen, Germany (W.S.). 2. From the Medizinische Klinik und Poliklinik I, Department of Cardiology (S.C., M.-L.v.B., K.S., I.K., S.F., R.C., F.G., K.R.L., M.L., A.T., C.S., S.M.), Walter-Brendel-Centre of Experimental Medicine (S.C., M.-L.v.B., J.-I.P., K.S., E.K., I.K., S.F., R.C., F.G., O.C., K.R.L., M.L., S.R., A.C.-M., A.T., L.P., C.S., E.D., S.M.), Department of Anaesthesiology (J.-I.P.), Department of Applied Physics (K.R.L.), and Institute of Pathology (G.A., J.M.-H.), Ludwig-Maximilians-Universität, Munich, Germany; DZHK (German Centre for Cardiovascular Research), Berlin, Germany (S.C., M.-L.v.B., K.S., I.K., S.F., R.C., F.G., K.R.L., M.L., A.T., C.S., S.M); Department of Biochemistry, Medical School, Justus-Liebig-University, Giessen, Germany (S.F.); Vascular Sciences, National Heart and Lung Institute, Faculty of Medicine, Hammersmith Campus, Imperial College London, South Kensington Campus, London, United Kingdom (R.S.); Department of Physiology and Biophysics, University of Arkansas for Medical Science, Little Rock (J.W.); Rudolf Virchow Center and DFG Research Center for Experimental Biomedicine, Universität Würzburg, Würzburg, Germany (B.N.); and Max Planck Institute for Heart and Lung Research, Giessen, Germany (W.S.). steffen.massberg@med.uni-muenchen.de.
Abstract
OBJECTIVE: Arteriogenesis is strongly dependent on the recruitment of leukocytes, especially monocytes, into the perivascular space of growing collateral vessels. On the basis of previous findings that platelets are central players in inflammatory processes and mediate the recruitment of leukocytes, the aim of this study was to assess the role of platelets in a model of arterial remodeling. APPROACH AND RESULTS: C57Bl6 wild-type mice, IL4-R/Iba mice lacking the extracellular domain of the glycoprotein Ibα (GPIbα) receptor, and mice treated with antibodies to block GPIbα or deplete circulating platelets were studied in peripheral arteriogenesis. Using a novel model of intravital 2-photon and epifluorescence imaging, we visualized and quantified the interaction of platelets with leukocytes and the vascular endothelium in vivo. We found that transient platelet adhesion to the endothelium of collateral vessels was a major event during arteriogenesis and depended on GPIbα. Furthermore, leukocyte recruitment was obviously affected in animals with defective platelet GPIbα function. In IL4-R/Iba mice, transient and firm leukocyte adhesion to the endothelium of collateral vessels, as well as leukocyte accumulation in the perivascular space, were significantly reduced. Furthermore, we detected platelet-leukocyte aggregates within the circulation, which were significantly reduced in IL4-R/Iba animals. Finally, platelet depletion and loss of GPIbα function resulted in poor reperfusion recovery as determined by laser Doppler imaging. CONCLUSIONS: Thus, GPIbα-mediated interactions between platelets and endothelial cells, as well as leukocytes, support innate immune cell recruitment and promote arteriogenesis-establishing platelets as critical players in this process.
OBJECTIVE: Arteriogenesis is strongly dependent on the recruitment of leukocytes, especially monocytes, into the perivascular space of growing collateral vessels. On the basis of previous findings that platelets are central players in inflammatory processes and mediate the recruitment of leukocytes, the aim of this study was to assess the role of platelets in a model of arterial remodeling. APPROACH AND RESULTS: C57Bl6 wild-type mice, IL4-R/Iba mice lacking the extracellular domain of the glycoprotein Ibα (GPIbα) receptor, and mice treated with antibodies to block GPIbα or deplete circulating platelets were studied in peripheral arteriogenesis. Using a novel model of intravital 2-photon and epifluorescence imaging, we visualized and quantified the interaction of platelets with leukocytes and the vascular endothelium in vivo. We found that transient platelet adhesion to the endothelium of collateral vessels was a major event during arteriogenesis and depended on GPIbα. Furthermore, leukocyte recruitment was obviously affected in animals with defective platelet GPIbα function. In IL4-R/Iba mice, transient and firm leukocyte adhesion to the endothelium of collateral vessels, as well as leukocyte accumulation in the perivascular space, were significantly reduced. Furthermore, we detected platelet-leukocyte aggregates within the circulation, which were significantly reduced in IL4-R/Iba animals. Finally, platelet depletion and loss of GPIbα function resulted in poor reperfusion recovery as determined by laser Doppler imaging. CONCLUSIONS: Thus, GPIbα-mediated interactions between platelets and endothelial cells, as well as leukocytes, support innate immune cell recruitment and promote arteriogenesis-establishing platelets as critical players in this process.
Authors: Xiaohong Ruby Xu; Naadiya Carrim; Miguel Antonio Dias Neves; Thomas McKeown; Tyler W Stratton; Rodrigo Matos Pinto Coelho; Xi Lei; Pingguo Chen; Jianhua Xu; Xiangrong Dai; Benjamin Xiaoyi Li; Heyu Ni Journal: Thromb J Date: 2016-10-04
Authors: Katrin Echtler; Ildiko Konrad; Michael Lorenz; Simon Schneider; Sebastian Hofmaier; Florian Plenagl; Konstantin Stark; Thomas Czermak; Anca Tirniceriu; Martin Eichhorn; Axel Walch; Georg Enders; Steffen Massberg; Christian Schulz Journal: PLoS One Date: 2017-03-02 Impact factor: 3.240
Authors: Michaela Finsterbusch; Waltraud C Schrottmaier; Julia B Kral-Pointner; Manuel Salzmann; Alice Assinger Journal: Platelets Date: 2018-02-20 Impact factor: 3.862
Authors: Anna-Kristina Kluever; Anna Braumandl; Silvia Fischer; Klaus T Preissner; Elisabeth Deindl Journal: Int J Mol Sci Date: 2019-12-07 Impact factor: 5.923