Adhesion of monocytes to vascular cell adhesion molecule-1-transduced human endothelial cells: implications for atherogenesis.
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 < or = 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.
Gerszten
R E
RE
Cardiovascular Research Center and Cardiac Unit, Massachusetts General Hospital, Boston, USA.
Lim
Y C
YC
Ding
H T
HT
Snapp
K
K
Kansas
G
G
Dichek
D A
DA
Cabañas
C
C
Sánchez-Madrid
F
F
Gimbrone
M A
MA
Rosenzweig
A
A
Luscinskas
F W
FW
D000260:Adenoviruses, Human; D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D002448:Cell Adhesion / Q000502:physiology*; D002460:Cell Line; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006801:Humans; D039441:Integrin alpha4; D019012:Integrin beta1 / Q000032:analysis; D019169:Jurkat Cells; D007668:Kidney; D019041:L-Selectin / Q000032:analysis; D008562:Membrane Glycoproteins / Q000032:analysis; D009000:Monocytes / Q000166:cytology / Q000502:physiology*; D019007:P-Selectin / Q000032:analysis; D011817:Rabbits; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology; D014162:Transfection; D014471:Umbilical Veins; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis / Q000502:physiology*
D015703:Antigens, CD; D019012:Integrin beta1; D008562:Membrane Glycoproteins; D019007:P-Selectin; C084882:P-selectin ligand protein; D019010:Vascular Cell Adhesion Molecule-1; D019041:L-Selectin; D039441:Integrin alpha4