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Circulation. 2001;103:1772-1777

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(Circulation. 2001;103:1772.)
© 2001 American Heart Association, Inc.


Basic Science Reports

RANTES Deposition by Platelets Triggers Monocyte Arrest on Inflamed and Atherosclerotic Endothelium

Philipp von Hundelshausen, BS; Kim S. C. Weber, MD; Yuqing Huo, MD; Amanda E. I. Proudfoot, PhD; Peter J. Nelson, PhD; Klaus Ley, MD; Christian Weber, MD

From the Institut für Prophylaxe der Kreislaufkrankheiten (P.v.H., K.S.C.W., C.W.) and Medizinische Poliklinik (P.J.N., C.W.), Ludwig-Maximilians-Universität, Munich, Germany; the Department of Biomedical Engineering (Y.H., K.L.), University of Virginia, Charlottesville; and the Serono Pharmaceutical Research Institute (A.E.I.P.), Geneva, Switzerland.

Correspondence to C. Weber, Institut für Prophylaxe der Kreislaufkrankheiten, Pettenkoferstrasse 9, 80336 München, Germany. E-mail christian.weber{at}klp.med.uni-muenchen.de

Background—Circulating platelets and chemoattractant proteins, such as the CC chemokine RANTES, contribute to the activation and interaction of monocytes and endothelium and may thereby play a pivotal role in the pathogenesis of inflammatory and atherosclerotic disease.

Methods and Results—The binding of RANTES to human endothelial cells was detected by ELISA or immunofluorescence after perfusion with platelets or exposure to their supernatants. Monocyte arrest on endothelial monolayers or surface-adherent platelets was studied with a parallel-wall flow chamber and video microscopy. We show that RANTES secreted by thrombin-stimulated platelets is immobilized on the surface of inflamed microvascular or aortic endothelium and triggers shear-resistant monocyte arrest under flow conditions, as shown by inhibition with the RANTES receptor antagonist Met-RANTES or a blocking RANTES antibody. Deposition of RANTES and its effects requires endothelial activation, eg, by interleukin-1ß, and is not supported by venous endothelium or adherent platelets. Immunohistochemistry revealed that RANTES is present on the luminal surface of carotid arteries of apolipoprotein E–deficient mice with early atherosclerotic lesions after wire-induced injury or cytokine exposure. In a mechanistic model of atherogenesis, monocyte adherence on endothelium covering such lesions was studied in murine carotid arteries perfused ex vivo, showing that the accumulation of monocytic cells in these carotid arteries involved RANTES receptors.

Conclusions—The deposition of RANTES by platelets triggers shear-resistant monocyte arrest on inflamed or atherosclerotic endothelium. Delivery of RANTES by platelets may epitomize a novel principle relevant to inflammatory or atherogenic monocyte recruitment from the circulation.


Key Words: inflammation • atherosclerosis • platelets • peptides • monocytes • blood flow




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[Abstract] [Full Text] [PDF]


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CirculationHome page
H. Koyama, T. Maeno, S. Fukumoto, T. Shoji, T. Yamane, H. Yokoyama, M. Emoto, T. Shoji, H. Tahara, M. Inaba, et al.
Platelet P-Selectin Expression Is Associated With Atherosclerotic Wall Thickness in Carotid Artery in Humans
Circulation, August 5, 2003; 108(5): 524 - 529.
[Abstract] [Full Text] [PDF]


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J. Immunol.Home page
H.-J. Anders, M. Frink, Y. Linde, B. Banas, M. Wornle, C. D. Cohen, V. Vielhauer, P. J. Nelson, H.-J. Grone, and D. Schlondorff
CC Chemokine Ligand 5/RANTES Chemokine Antagonists Aggravate Glomerulonephritis Despite Reduction of Glomerular Leukocyte Infiltration
J. Immunol., June 1, 2003; 170(11): 5658 - 5666.
[Abstract] [Full Text] [PDF]


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BloodHome page
P. C. Burger and D. D. Wagner
Platelet P-selectin facilitates atherosclerotic lesion development
Blood, April 1, 2003; 101(7): 2661 - 2666.
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Diabetes CareHome page
K. Nakajima, Y. Tanaka, T. Nomiyama, T. Ogihara, F. Ikeda, R. Kanno, N. Iwashita, K. Sakai, H. Watada, T. Onuma, et al.
RANTES Promoter Genotype Is Associated With Diabetic Nephropathy in Type 2 Diabetic Subjects
Diabetes Care, March 1, 2003; 26(3): 892 - 898.
[Abstract] [Full Text] [PDF]


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CirculationHome page
A. Schober, D. Manka, P. von Hundelshausen, Y. Huo, P. Hanrath, I. J. Sarembock, K. Ley, and C. Weber
Deposition of Platelet RANTES Triggering Monocyte Recruitment Requires P-Selectin and Is Involved in Neointima Formation After Arterial Injury
Circulation, September 17, 2002; 106(12): 1523 - 1529.
[Abstract] [Full Text] [PDF]


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Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
T. S. Olson and K. Ley
Chemokines and chemokine receptors in leukocyte trafficking
Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2002; 283(1): R7 - R28.
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HeartHome page
P. AUKRUST, T. WAeHRE, J. K. DAMAS, L. GULLESTAD, and N. O. SOLUM
Inflammatory role of platelets in acute coronary syndromes
Heart, December 1, 2001; 86(6): 605 - 606.
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CirculationHome page
P. Libby and D. I. Simon
Inflammation and Thrombosis : The Clot Thickens
Circulation, April 3, 2001; 103(13): 1718 - 1720.
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