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Published on: July 23, 2012
Pocket proteins p107 and p130 exhibit increased expression in macrophages during SIV encephalitis
Elizabeth M Chalovich1, Maya A Koike, Mandar A Aras
1Department of Pathology, Division of Neuropathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Abstract:
Progression of HIV encephalitis (HIVE) is associated with neuronal damage and loss because of infiltration of infected and/or activated macrophages into the CNS. We have previously observed increased inactivation of the retinoblastoma susceptibility gene product (pRb) by phosphorylation in neurons and glia of HIVE and the simian model of HIVE (SIVE). To determine if other pRb family members are altered in response to increased macrophage-secreted factors, we investigated expression of pRb family members p107 and p130 in SIVE. Both p130 and p107 exhibited increased staining in macrophages, but not neurons, astrocytes or T-cells in SIVE. Increased p130 and p107 immunostaining was not limited to virally infected or PCNA-expressing macrophages. Most p107-positive staining was observed in perivascular macrophages, suggesting p107 may indicate macrophages at a specific stage of differentiation soon after migration. In contrast, cytoplasmic p130 was found in the majority of macrophages present in SIVE cases and may indicate activation as it was not seen in microglia in control CNS. These findings suggest that p107 and p130 are differentially expressed in CNS macrophage populations which may have multiple derivations and/or roles in lentiviral encephalitis.
Insights
HIV encephalitis (HIVE) involves brain damage. Researchers found p107 and p130 proteins are altered in macrophages during simian HIVE, suggesting roles in lentiviral encephalitis progression.
Area of Science:
- Neuroscience
- Immunology
- Molecular Biology
Background:
- HIV encephalitis (HIVE) causes neuronal damage due to macrophage infiltration in the central nervous system (CNS).
- Previous studies noted altered retinoblastoma susceptibility gene product (pRb) in HIVE and its simian model (SIVE).
Purpose of the Study:
- To investigate the expression of pRb family members, p107 and p130, in the SIVE model.
- To understand the role of these proteins in CNS macrophages during lentiviral encephalitis.
Main Methods:
- Immunohistochemical analysis of CNS tissues from SIVE model.
- Examination of p107 and p130 expression in various cell types, including macrophages, neurons, astrocytes, and T-cells.
- Correlation of p107/p130 staining with macrophage activation markers (e.g., PCNA) and location.
Main Results:
- Both p107 and p130 showed increased immunostaining in macrophages within the SIVE CNS.
- p107 staining was prominent in perivascular macrophages, potentially indicating a specific differentiation stage.
- Cytoplasmic p130 was abundant in most SIVE macrophages, suggesting activation and differentiating it from control microglia.
Conclusions:
- p107 and p130 are differentially expressed in CNS macrophage populations during lentiviral encephalitis.
- These proteins may play distinct roles in macrophage differentiation and activation within the infected CNS.
- Understanding these alterations could offer insights into HIVE pathogenesis and potential therapeutic targets.
