Osteopontin prevents monocyte recirculation and apoptosis

Abstract: Cells of the monocyte/macrophage lin-eage have been shown to be the principal targets for productive HIV-1 replication within the CNS. In addition, HIV-1-associated dementia (HAD) has been shown to correlate with macrophage abun-dance in the brain. Although increased entry of monocytes into the brain is thought to initiate this process, mechanisms that prevent macrophage egress from the brain and means that prevent mac-rophage death may also contribute to cell accumu-lation. We hypothesized that osteopontin (OPN) was involved in the accumulation of macrophages in the brain in neuroAIDS. Using in vitro model systems, we have demonstrated the role of OPN in two distinct aspects of macrophage accumulation: prevention from recirculation and protection from apoptosis. In these unique mechanisms, OPN would aid in macrophage survival and accumula-tion in the brain, the pathological substrate o