SUMMARY:Human immunodeficiency virus type 1 (HIV-1) infection is often associated with central nervous system damage and vascular complications. However, the mechanisms of this association are largely unknown. We examined the effect of HIV-1 envelope glycoprotein 120 (gp120) on cell adhesion molecule expression by endothelial cells. We found, for the first time, that both soluble and membrane-bound gp120 could significantly increase the expression of human endothelial intercellular adhesion molecule-1 (ICAM-1) at both mRNA and protein levels, but not vascular cell adhesion molecule-1 and E-selectin. The specificity of gp120-mediated response was demonstrated by blocking experiments using a specific monoclonal antibody against gp120, which successfully abolished the gp120-mediated increase of ICAM-1 expression. Furthermore, there was a significant increase of human monocytic cell line THP-1 adherence onto the gp120-treated endothelial monolayers. This increased cell adhesion was effectively blocked by either anti-gp120 or anti-ICAM antibodies. These findings suggest that HIV-1 gp120-mediated endothelial ICAM-1 expression could be one of the important mechanisms of HIV-1 pathogenesis. (Lab Invest 2002, 82:245-255).
B oth human immunodeficiency virus (HIV)-positiveand acquired immune deficiency syndrome (AIDS) patients often have significantly increased levels of circulating cell adhesion molecules, such as intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1) (Greenwood et al, 1998; Seigneur et al, 1997). Serum ICAM-1 levels correlate well with AIDS progression in HIV type 1 (HIV-1)-infected patients (Galea et al, 1997). Endothelial cells and leukocytes from these patients exhibit a significant increase of such adhesion molecules (Pillet et al, 1999;Zietz et al, 1996). HIV-1 particles also incorporate many cell adhesion molecules (Guo and Hildreth, 1995). HIV-associated ICAM-1 is biologically active and can enhance virus infectivity (Fortin et al, 1997) and virus-induced syncytium formation (Gruber et al, 1991). ICAM-1-bearing viruses are less susceptible to neutralization by anti-envelope glycoprotein 120 (gp120) monoclonal antibodies than the same virus produced in cells expressing no ICAM-1 (Sawyer et al, 1994). HIV-1 replication in monocytes/macrophages is significantly enhanced by interaction with endothelial cells through cell adhesion molecules (Gilles et al, 1995). In addition, alterations in expression of cell adhesion molecules by leukocytes and endothelial cells can increase leukocyte migration into the tissues, which may result in certain organ damage. Indeed, HIV-1-infected leukocytes can transmigrate into the central nervous system and cause encephalopathy (Nottet, 1999). Endothelial cell dysfunction and leukocyte infiltration may also be attributable to the increased frequency of vascular complications such as atherosclerosis in HIV-1-infected patients (Constans et al, 1995;Tabib et al, 2000).Several factors may contribute to the increased levels of cell adhesion mole...