CD163, A MARKER OF PERIVASCULAR MACROPHAGES IS UPREGULATED ON MICROGLIA IN SIVE

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Macrophages and microglia are the major cell types infected in the central nervous system of humans infected with HIV and macaques infected with SIV. Microglia are the resident macrophages of the brain and have been shown to be quite sensitive to even minor disturbances of central nervous system (CNS) homeostasis, and are readily activated. Activation of microglia induces changes in cellular morphology and in the expression of cell surface receptors. CD163 is a member of the scavenger receptor family with cysteine-rich domains (SCRC) identified as a receptor of haptoglobin-hemoglobin (Hp-Hb) complex and exclusively expressed by cells of monocyte-macrophage lineage. We examined the expression of CD163 in vitro and in vivo by multiple techniques and at varying times after SIV infection in animals with or without SIVE. Our data show that CD163 is expressed by cells of monocyte/macrophage lineage including perivascular macrophages but not parenchymal microglia in normal and acutely SIV-infected animals or animals with terminal AIDS without encephalitis. CD163 expression was detected in activated microglia (HLA-DR+) surrounding SIVE lesions in chronically infected macaques with severe encephalitis in the presence of haptoglobin-haemoglobin complex (Hp-Hb) in the tissue suggesting breakdown of the blood-brain-barrier. CD163 expression was also induced in microglia in vitro by stimulation with Hp-Hb complex indicating that the interaction of the Hp-Hb complex is required to trigger the upregulation of CD163. To confirm that activation of microglia was associated with the presence and upregulation of CD163 RNA we treated microglia isolated from rhesus macaque brain with Hp-Hb for 0, 6, 12, 18 and 48 h and performed quantitative real-time PCR. We observed a 2.5 fold increase of CD163 RNA in the microglia treated with haptoglobin-hemoglobin within 18hrs of exposure. We conclude that CD163 is a selective marker of perivascular macrophages in normal macaques and during the early phases of SIV infection. However, latter in infection CD163 also labels microglia that have been activated probably as a result of vascular compromise.