RANTES deposition by platelets triggers monocyte arrest on inflamed and atherosclerotic endothelium

Philipp Von Hundelshausen, Kim S.C. Weber, Yuqing Huo, Amanda E.I. Proudfoot, Peter J. Nelson, Klaus Ley, Christian Weber

Research output: Contribution to journalArticle

437 Citations (Scopus)

Abstract

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-1β, 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.

Original languageEnglish (US)
Pages (from-to)1772-1777
Number of pages6
JournalCirculation
Volume103
Issue number13
DOIs
StatePublished - Apr 3 2001
Externally publishedYes

Fingerprint

Chemokine CCL5
Endothelium
Monocytes
Blood Platelets
Carotid Arteries
Video Microscopy
CC Chemokines
Blocking Antibodies
Chemotactic Factors
Apolipoproteins E
Interleukin-1
Thrombin
Fluorescent Antibody Technique
Atherosclerosis
Endothelial Cells
Perfusion
Enzyme-Linked Immunosorbent Assay
Immunohistochemistry
Cytokines

Keywords

  • Atherosclerosis
  • Blood flow
  • Inflammation
  • Monocytes
  • Peptides
  • Platelets

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Von Hundelshausen, P., Weber, K. S. C., Huo, Y., Proudfoot, A. E. I., Nelson, P. J., Ley, K., & Weber, C. (2001). RANTES deposition by platelets triggers monocyte arrest on inflamed and atherosclerotic endothelium. Circulation, 103(13), 1772-1777. https://doi.org/10.1161/01.CIR.103.13.1772

RANTES deposition by platelets triggers monocyte arrest on inflamed and atherosclerotic endothelium. / Von Hundelshausen, Philipp; Weber, Kim S.C.; Huo, Yuqing; Proudfoot, Amanda E.I.; Nelson, Peter J.; Ley, Klaus; Weber, Christian.

In: Circulation, Vol. 103, No. 13, 03.04.2001, p. 1772-1777.

Research output: Contribution to journalArticle

Von Hundelshausen, P, Weber, KSC, Huo, Y, Proudfoot, AEI, Nelson, PJ, Ley, K & Weber, C 2001, 'RANTES deposition by platelets triggers monocyte arrest on inflamed and atherosclerotic endothelium', Circulation, vol. 103, no. 13, pp. 1772-1777. https://doi.org/10.1161/01.CIR.103.13.1772
Von Hundelshausen, Philipp ; Weber, Kim S.C. ; Huo, Yuqing ; Proudfoot, Amanda E.I. ; Nelson, Peter J. ; Ley, Klaus ; Weber, Christian. / RANTES deposition by platelets triggers monocyte arrest on inflamed and atherosclerotic endothelium. In: Circulation. 2001 ; Vol. 103, No. 13. pp. 1772-1777.
@article{58792c4731b8426ba4b398327fbefbda,
title = "RANTES deposition by platelets triggers monocyte arrest on inflamed and atherosclerotic endothelium",
abstract = "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-1β, 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.",
keywords = "Atherosclerosis, Blood flow, Inflammation, Monocytes, Peptides, Platelets",
author = "{Von Hundelshausen}, Philipp and Weber, {Kim S.C.} and Yuqing Huo and Proudfoot, {Amanda E.I.} and Nelson, {Peter J.} and Klaus Ley and Christian Weber",
year = "2001",
month = "4",
day = "3",
doi = "10.1161/01.CIR.103.13.1772",
language = "English (US)",
volume = "103",
pages = "1772--1777",
journal = "Circulation",
issn = "0009-7322",
publisher = "Lippincott Williams and Wilkins",
number = "13",

}

TY - JOUR

T1 - RANTES deposition by platelets triggers monocyte arrest on inflamed and atherosclerotic endothelium

AU - Von Hundelshausen, Philipp

AU - Weber, Kim S.C.

AU - Huo, Yuqing

AU - Proudfoot, Amanda E.I.

AU - Nelson, Peter J.

AU - Ley, Klaus

AU - Weber, Christian

PY - 2001/4/3

Y1 - 2001/4/3

N2 - 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-1β, 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.

AB - 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-1β, 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.

KW - Atherosclerosis

KW - Blood flow

KW - Inflammation

KW - Monocytes

KW - Peptides

KW - Platelets

UR - http://www.scopus.com/inward/record.url?scp=0035799376&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035799376&partnerID=8YFLogxK

U2 - 10.1161/01.CIR.103.13.1772

DO - 10.1161/01.CIR.103.13.1772

M3 - Article

C2 - 11282909

AN - SCOPUS:0035799376

VL - 103

SP - 1772

EP - 1777

JO - Circulation

JF - Circulation

SN - 0009-7322

IS - 13

ER -