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The chemokine KC, but not monocyte chemoattractant protein-1, triggers monocyte arrest on early atherosclerotic endothelium
Open accessAbstract
In a reconstituted flow chamber system, preincubation with chemokines can trigger the arrest of rolling monocytes, suggesting that this interaction could help recruit these cells to early atherosclerotic lesions. To date, however, the contribution of endothelium-derived chemokines found in these lesion to monocyte arrests has not been investigated. The endothelium of lesion-prone carotid arteries from apolipoprotein E-deficient (ApoE(-/-)) mice, but not control mice, presents the chemokines KC (mouse GRO-alpha) and JE (mouse monocyte chemoattractant protein-1 [MCP-1]). Arrest of a monocytic cell line or mouse blood monocytes perfused through carotid arteries of ApoE(-/-) mice was reduced by treating with either pertussis toxin, an antagonist of CXCR2, or an antibody to KC, but this process was insensitive to agents that blocked CCR-2 or JE. Conversely, monocyte accumulation more than doubled upon pre-perfusion of the carotid artery with KC but not with mouse MCP-1. Blockade of alpha(4)beta(1) integrin (VLA-4) or vascular cell adhesion molecule-1, but not CD18 or intercellular adhesion molecule-1, almost completely inhibited the arrest of monocytes. We conclude that when presented by early atherosclerotic lesions, KC but not murine MCP-1 triggers VLA-4-dependent monocyte recruitment.
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“Additionally, recent studies showed effects of KC expression on monocyte recruitment during development of experimental atherosclerosis (47).”
From The IL-6–gp130–STAT3 pathway in hepatocytes triggers liver protection in T cell–mediated liver injury (2005) · cites this paper as [47]
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Metadata
- Authors
- Huo, Y., Weber, C., Forlow, S. B., Sperandio, M., Thatte, J., Mack, M., Jung, S., Littman, D. R., & Ley, K.
- Affiliations
- University of Virginia (US)
- RWTH Aachen University (DE)
- Ludwig-Maximilians-Universität München (DE)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Ley, Klaus
- ORCID
- Venue
- Journal of Clinical Investigation
- Published
- 2001-11-01
- Volume
- 108
- Issue
- 9
- Pages
- 1307-1314
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC209441
- OpenAlex
- W2117908470
- Cited by
- 266
- References
- 50
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 2 · 2023: 1 · 2022: 5 · 2021: 4 · 2020: 5 · 2019: 4 · 2018: 6 · 2017: 8 · 2016: 5 · 2015: 11 · 2014: 9 · 2013: 12 · 2012: 17
- FWCI
- 5.30
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- RWTH Publications (RWTH Aachen) (submittedVersion)
- Funders
- American Heart Association (HL-58108)
- Deutsche Forschungsgemeinschaft
- University of British Columbia
- National Institutes of Health (58108)
- National Heart, Lung, and Blood Institute (HL 58108, R01HL058108)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Keywords
- MCP-1, atherosclerosis, CXCR2, VLA-4, alpha4beta1 integrin, monocyte recruitment, ApoE-deficient mice, carotid artery, pertussis toxin, CCR2, VCAM-1, CD18, ICAM-1
- MeSH terms
- Animals, Antibodies, Monoclonal, Arteriosclerosis, Carotid Arteries, Cell Adhesion, Cell Line, Chemotactic Factors, Endothelium, Vascular, Growth Substances, Humans, Mice, Inbred C57BL, Monocytes, Virulence Factors, Bordetella, Protein Binding, Time Factors, Integrins, Receptors, Lymphocyte Homing, CD18 Antigens, Chemokine CCL2, Chemokines, CXC, Receptors, Interleukin-8B, Intercellular Signaling Peptides and Proteins, Pertussis Toxin, Integrin alpha4beta1, Mice, Rats, Chemokine CXCL1
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