MONOCYTE ADHESION TO ENDOTHELIUM IN SIMIAN IMMUNODEFICIENCY VIRUS-INDUCED AIDS ENCEPHALITIS IS MEDIATED BY VASCULAR CELL-ADHESION MOLECULE-1 ALPHA-4-BETA-1 INTEGRIN INTERACTIONS/

Because the mechanisms associated with recruitment of monocytes to bra in in AIDS encephalitis are unknown, we used tissues front rhesus monk eys infected with simian immunodeficiency virus (SIV) to examine the r elative contributions of various adhesion Pathways in mediating monocy te adhesion to endothelium from encephalitic brain. Using a modified S tamper and Woodruff tissue adhesion assay, we found that the human mon ocytic cell lines, THP-1 and U937, and the B cell fine, Ramos, Prefere ntially bound to brain vessels from monkeys with AIDS encephalitis. Us ing a combined tissue adhesion/ immunohistochemistry approach, these c ells only bound to vessels expressing vascular cell adhesion molecule- 1 (VCAM-1). Furthermore, pretreatment of tissues with antibodies to VC AM-1 or cell lines with antibodies to VLA-4 (CD49d) inhibited adhesion by more than 70%. Intercellular adhesion molecule-1 (ICAM-1)/beta 2 i ntegrin interactions were not significant in mediating cell adhesion t o the vasculature in encephalitic simian brain using a cell line (JY) capable of binding rhesus monkey ICAM-1. In addition, selectin-mediate d interactions did not significantly contribute to cell binding to enc ephalitic brain as there was no immunohistochemical expression of E-se lectin and P-selectin in either normal or encephalitic brain, nor was there a demonstrable adhesive effect from L-selectin using L-selectin- transfected 300.19 cells on simian encephalitic brain These results de monstrate that using the tissue adhesion assay, TNP-1, U337, and Ramos cells bind to vessels in brain from animals with AIDS encephalitis us ing VCAM-1/alpha 4 beta 1 integrin interactions and suggest that VCAM- 1 and VLA-4 may be integral for monocyte recruitment to the central ne rvous system during the development of AIDS encephalitis.