Osteopontin prevents monocyte recirculation and apoptosis.
Cells of the monocyte/macrophage lineage 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 abundance 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 macrophage death may also contribute to cell accumulation. 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 accumulation in the brain, the pathological substrate of HAD.
Burdo
Tricia H
TH
Molecular and Integrative Neurosciences Department, The Scripps Research Institute, 10550 North Torrey Pines Rd., SP30-2030, La Jolla, CA 92037, USA.
Wood
Malcolm R
MR
Fox
Howard S
HS
D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism; D002634:Chemotaxis, Leukocyte; D018792:Encephalitis, Viral / Q000097:blood / Q000134:cerebrospinal fluid; D042783:Endothelial Cells / Q000502:physiology; D006801:Humans; D008253:Macaca mulatta; D008262:Macrophage Activation; D008264:Macrophages / Q000502:physiology*; D009000:Monocytes / Q000502:physiology*; D053495:Osteopontin / Q000097:blood / Q000134:cerebrospinal fluid / Q000502:physiology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000097:blood / Q000134:cerebrospinal fluid
D018925:Chemokines; D053495:Osteopontin