ADHESION OF MONOCYTES TO VASCULAR CELL-ADHESION MOLECULE-1-TRANSDUCEDHUMAN ENDOTHELIAL-CELLS - IMPLICATIONS FOR ATHEROGENESIS

To study the role of vascular cell adhesion molecule-1 (VCAM-1) in mon ocyte recruitment and atherogenesis, we constructed a recombinant aden ovirus, AdRSVrVCAM-1, carrying the rabbit VCAM-1 cDNA. We have previou sly shown that AdRSVrVCAM-1-transduced human umbilical vein endothelia l cells (HUVECs) support the adhesion of CD4(+) CD45RO(+) memory T lym phocytes under laminar flow conditions. We now demonstrate that AdRSVr VCAM-1-transduced HUVECs support the adhesion of peripheral blood mono cytes at a sheer stress of less than or equal to 1.5 dyne/cm(2). Altho ugh VCAM-1 supported only firm adhesion of lymphocytes, it was able to mediate monocyte rolling, firm adhesion, and transmigration when expr essed in the context of otherwise unactivated vascular endothelium. VC AM-1-transduced HUVECs supported the adhesion of as many as 4-fold mor e monocytes than T cells under laminar flow. The greater monocyte adhe sion was explained at least in part by leukocyte-leukocyte interaction s (secondary adhesions), which were not seen with T cells. These secon dary monocyte interactions were specifically blocked by monoclonal ant ibodies to L-selectin and P-selectin glycoprotein ligand-1. These data demonstrate that VCAM-1 expressed in the context of unactivated vascu lar endothelium supports the adhesion of the leukocyte populations pre sent in atherosclerotic plaque and may contribute to the predominance of monocytes over lymphocytes.