PHENOTYPIC AND FUNCTIONAL ACTIVATION OF MONOCYTES IN HIV-1 INFECTION - INTERACTIONS WITH NEURAL CELLS

To investigate mechanisms that facilitate transendothelial migration o f HIV-infected leukocytes and their interactions with neural tissues e arly in the disease, we studied peripheral blood from Centers for Dise ase Control class A patients. Patients' monocytes displayed increased quantities of the adhesion molecules CD11a, CD11b, and very late antig en 4 (VLA-4). Expression of these correlated directly with the numbers of monocytes that migrated through confluent endothelium. These ligan ds also mediated leukocyte interactions with cultured human neural cel l lines. Although patients' cells bound in greater numbers, there was no evidence of target cell injury. To evaluate the direct effect of HI V-l on monocyte neuroadhesion, we compared infected with uninfected mo nocytoid (U-937;THP-1) and T lymphoblastoid (MT-4) cell lines. HIV inf ection increased the neuroadhesiveness of monocytoid lines only. By us ing lines with more than 95 % HIV-infected cells, we demonstrated that HIV-1 gp120 participates with lymphocyte function-associated antigen 1 and VLA-4 to mediate monocyte-neural cell interactions.