Adhesion of monocytes to vascular cell adhesion molecule-1-transduced human endothelial cells: Implications for atherogenesis

Robert E. Gerszten, Yaw Chyn Lim, Han T. Ding, Karen Snapp, Geoffrey Kansas, David A. Dichek, Carlos Cabañas, Francisco Sánchez-Madrid, Michael A. Gimbrone, Anthony Rosenzweig, Francis W. Luscinskas*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

89 Scopus citations

Abstract

To study the role of vascular cell adhesion molecule-1 (VCAM-1) in monocyte recruitment and atherogenesis, we constructed a recombinant adenovirus, AdRSVrVCAM-1, carrying the rabbit VCAM-1 cDNA. We have previously shown that AdRSVrVCAM-1-transduced human umbilical vein endothelial cells (HUVECs) support the adhesion of CD4+ CD45RO+ memory T lymphocytes under laminar flow conditions. We now demonstrate that AdRSVrVCAM-1-transduced HUVECs support the adhesion of peripheral blood monocytes at a shear stress of ≤1.5 dyne/cm2. Although VCAM-1 supported only firm adhesion of lymphocytes, it was able to mediate monocyte rolling, firm adhesion, and transmigration when expressed in the context of otherwise unactivated vascular endothelium. VCAM-1-transduced HUVECs supported the adhesion of as many as 4-fold more monocytes than T cells under laminar flow. The greater monocyte adhesion was explained at least in part by leukocyte-leukocyte interactions (secondary adhesions), which were not seen with T cells. These secondary monocyte interactions were specifically blocked by monoclonal antibodies to L-selectin and P-selectin glycoprotein ligand-1. These data demonstrate that VCAM-1 expressed in the context of unactivated vascular endothelium supports the adhesion of the leukocyte populations present in atherosclerotic plaque and may contribute to the predominance of monocytes over lymphocytes.

Original languageEnglish (US)
Pages (from-to)871-878
Number of pages8
JournalCirculation research
Volume82
Issue number8
DOIs
StatePublished - May 4 1998

Keywords

  • Adenovirus
  • Adhesion
  • Atherosclerosis
  • Mononuclear leukocyte

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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