TY - JOUR
T1 - Adhesion of monocytes to vascular cell adhesion molecule-1-transduced human endothelial cells
T2 - Implications for atherogenesis
AU - Gerszten, Robert E.
AU - Lim, Yaw Chyn
AU - Ding, Han T.
AU - Snapp, Karen
AU - Kansas, Geoffrey
AU - Dichek, David A.
AU - Cabañas, Carlos
AU - Sánchez-Madrid, Francisco
AU - Gimbrone, Michael A.
AU - Rosenzweig, Anthony
AU - Luscinskas, Francis W.
PY - 1998/5/4
Y1 - 1998/5/4
N2 - 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.
AB - 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.
KW - Adenovirus
KW - Adhesion
KW - Atherosclerosis
KW - Mononuclear leukocyte
UR - http://www.scopus.com/inward/record.url?scp=0032482139&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032482139&partnerID=8YFLogxK
U2 - 10.1161/01.RES.82.8.871
DO - 10.1161/01.RES.82.8.871
M3 - Article
C2 - 9580553
AN - SCOPUS:0032482139
SN - 0009-7330
VL - 82
SP - 871
EP - 878
JO - Circulation research
JF - Circulation research
IS - 8
ER -