Cited by 243Cell Adhesion Molecules ResearchConnective Tissue Growth Factor ResearchAtherosclerosis and Cardiovascular Diseases

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Identification of integrin αMβ2 as an adhesion receptor on peripheral blood monocytes for Cyr61 (CCN1) and connective tissue growth factor (CCN2): immediate-early gene products expressed in atherosclerotic lesions

Schober, Joseph M., Chen, Ningyu, Grzeszkiewicz, Tatiana M., Jovanovic, Igor, Emeson, Eugene E., Ugarova, Tatiana P., Ye, Richard D., Lau, Lester F., Lam, Stephen C.-T.·2002·Blood

DOI 10.1182/blood.v99.12.4457

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Abstract

Cysteine-rich 61 (Cyr61, CCN1) and connective tissue growth factor (CTGF, CCN2) are growth factor–inducible immediate-early gene products found in blood vessel walls and healing cutaneous wounds. We previously reported that the adhesion of endothelial cells, platelets, and fibroblasts to these extracellular matrix–associated proteins is mediated through integrin receptors. In this study, we demonstrated that both Cyr61 and CTGF are expressed in advanced atherosclerotic lesions of apolipoprotein E–deficient mice. Because monocyte adhesion and transmigration are important for atherosclerosis, wound healing, and inflammation, we examined the interaction of THP-1 monocytic cells and isolated peripheral blood monocytes with Cyr61 and CTGF. THP-1 cells and monocytes adhered to Cyr61- or CTGF-coated wells in an activation-dependent manner and this process was mediated primarily through integrin αMβ2. Additionally, expression of αMβ2 on human embryonic kidney 293 cells resulted in enhanced cell adhesion to Cyr61. Consistent with these data, a GST-fusion protein containing the I domain of the integrin αM subunit bound specifically to immobilized Cyr61 or CTGF. We have also investigated the requirement of cell surface heparan sulfate proteoglycans (HSPGs) as coreceptors for monocyte adhesion to Cyr61. Pretreatment of monocytes with heparin or heparinase I resulted in partial inhibition of cell adhesion to Cyr61. However, monocytes, but not fibroblasts, were capable of adhering to a Cyr61 mutant deficient in heparin binding activity. Collectively, these results show that activated monocytes adhere to Cyr61 and CTGF through integrin αMβ2 and cell surface HSPGs. However, unlike fibroblast adhesion to Cyr61, cell surface HSPGs are not absolutely required for this adhesion process.

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Authors: Schober, J. M., Chen, N., Grzeszkiewicz, T. M., Jovanovic, I., Emeson, E. E., Ugarova, T. P., Ye, R. D., Lau, L. F., & Lam, S. C.-T.
Affiliations: Cleveland Clinic (US)
ORCID: Schober, Joseph M.
Chen, Ningyu
Ugarova, Tatiana P.
Ye, Richard D.
Lau, Lester F.
Lam, Stephen C.-T.
Venue: Blood
Publisher: American Society of Hematology
Published: 2002-06-15
Volume: 99
Issue: 12
Pages: 4457-4465
ISSN: 0006-4971 (ISSN-L)
1528-0020
DOI: 10.1182/blood.v99.12.4457
OpenAlex: W2048563910
Cited by: 242
References: 54
Citations by year: 2026: 4 · 2025: 4 · 2024: 6 · 2023: 7 · 2022: 6 · 2021: 15 · 2020: 8 · 2019: 12 · 2018: 8 · 2017: 11 · 2016: 14 · 2015: 9 · 2014: 8 · 2013: 11 · 2012: 10
FWCI: 8.83
Type: journal article
Language: en
Open access: closed
Locations: Blood (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (5r01ca080080-05)
National Heart, Lung, and Blood Institute (HL07829, HL41793, HL 63199, R01HL063199)
National Cancer Institute (CA-80080, R01CA046565, CA-46565)
Topics: Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connective Tissue Growth Factor Research
Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
Keywords: Mac-1, CYR61, connective tissue growth factor, monocyte adhesion, monocyte transmigration, atherosclerosis, heparan sulfate proteoglycans, ApoE-deficient mice, THP-1 cells, integrin I domain, cell adhesion, wound healing
MeSH terms: Animals, Apolipoproteins E, Arteriosclerosis, Cell Adhesion, Disease Models, Animal, Growth Substances, Humans, Immunohistochemistry, Monocytes, Protein Binding, Integrins, Macrophage-1 Antigen, Protein Structure, Tertiary, Immediate-Early Proteins, Mice, Knockout, Intercellular Signaling Peptides and Proteins, Mice, Connective Tissue Growth Factor, Cysteine-Rich Protein 61

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Identification of integrin αMβ2 as an adhesion receptor on peripheral blood monocytes for Cyr61 (CCN1) and connective tissue growth factor (CCN2): immediate-early gene products expressed in atherosclerotic lesions

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