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MCP-1 and IL-8 trigger firm adhesion of monocytes to vascular endothelium under flow conditions

Nature volume 398, pages 718–723 (1999)Cite this article

Abstract

Monocytes contribute to the development of atherosclerotic lesions in mouse models1,3. The chemoattractant proteins (chemokines), monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8), are found in human atheroma4,5, and mice lacking receptors for these chemokines are less susceptible to atherosclerosis and have fewer monocytes in vascular lesions6,7. Although MCP-1 has a powerful effect on monocytes, IL-8 is thought to act predominantly on neutrophils and it is unclear howit could recruit monocytes6,8. Here we investigate the ability of chemokines to control the interaction of monocytes under flow conditions with vascular endothelium that has been transduced to express specific leukocyte-adherence receptors. We find that MCP-1 and IL-8 can each rapidly cause rolling monocytes to adhere firmly onto monolayers expressing E-selectin, whereas related chemokines do not. These effects do not correlate with either the induction of a calcium transient or chemotaxis. We conclude that chemokines are important modulators of monocyte–endothelial interactions under flow conditions. Moreover, our finding that IL-8 is a powerful trigger for firm adhesion of monocytes to vascular endothelium reveals an unexpected role for this chemokine in monocyte recruitment.

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Figure 1: Monocyte attachment to adenovirally transduced or cytokine-activated HUVEC.
Figure 2: MCP-1 and IL-8 induce arrest of monocytes.
Figure 3: MCP-1 and IL-8 augment arrest by using different integrins.
Figure 4: Chemokine-induced calcium flux in human monocytes.
Figure 5: Chemotaxis of elutriated monocytes.
Figure 6: Monocytes express functional IL-8 receptors.

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Acknowledgements

We thank K. Case and W. Atkinson for preparation of human endothelial cell cultures; L. Li and Q. Qui for technical assistance; P. Kaltofen for help with manuscript preparation; M.Cybulsky for rabbit VCAM-1 cDNA and antibody Rb1/9; D. Dichek for help in construction of AdVCAM-1 and for AdRSV β-gal; Leukosite for antibody 2D7; I. Charo for reviewing the manuscript; Z.N. Demirjian and other members of the MGH Clinical Hematology Laboratory for their review of leukocyte morphology. We acknowledge support from the NIH (R.E.G., A.R., M.A.G., F.W.L., A.D.L.). A.R. is an Established Investigator of the American Heart Association.

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Authors and Affiliations

  1. The Cardiovascular Research Center and Cardiology Division, Massachusetts General Hospital, Boston, 02114, Massachusetts, USA

    Robert E. Gerszten & Anthony Rosenzweig

  2. Harvard Medical School, Boston, 02114, Massachusetts, USA

    Robert E. Gerszten, Eduardo A. Garcia-Zepeda, Yaw-Chyn Lim, Michael A. Gimbrone Jr, Andrew D. Luster, Francis W. Luscinskas & Anthony Rosenzweig

  3. Infectious Disease Unit, Massachusetts General Hospital, Boston, 02114, Massachusetts, USA

    Eduardo A. Garcia-Zepeda & Andrew D. Luster

  4. Vascular Research Division, Department of Pathology, Brigham and Women's Hospital, Boston, 02115, Massachusetts, USA

    Yaw-Chyn Lim, Han A. Ding, Michael A. Gimbrone Jr & Francis W. Luscinskas

  5. Molecular Genetics, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan

    Masayuki Yoshida

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  1. Robert E. Gerszten
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Correspondence to Anthony Rosenzweig.

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Gerszten, R., Garcia-Zepeda, E., Lim, YC. et al. MCP-1 and IL-8 trigger firm adhesion of monocytes to vascular endothelium under flow conditions. Nature 398, 718–723 (1999). https://doi.org/10.1038/19546

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