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Updated: May 5, 2026
Isolation of Brain and Spinal Cord Mononuclear Cells Using Percoll Gradients
Published on: February 3, 2011
Increased monocyte turnover from bone marrow correlates with severity of SIV encephalitis and CD163 levels in plasma
Tricia H Burdo1, Caroline Soulas, Krystyna Orzechowski
1Biology Department, Boston College, Chestnut Hill, Massachusetts, United States of America.
Abstract:
Cells of the myeloid lineage are significant targets for human immunodeficiency virus (HIV) in humans and simian immunodeficiency virus (SIV) in monkeys. Monocytes play critical roles in innate and adaptive immunity during inflammation. We hypothesize that specific subsets of monocytes expand with AIDS and drive central nervous system (CNS) disease. Additionally, there may be expansion of cells from the bone marrow through blood with subsequent macrophage accumulation in tissues driving pathogenesis. To identify monocytes that recently emigrated from bone marrow, we used 5-bromo-2'-deoxyuridine (BrdU) labeling in a longitudinal study of SIV-infected CD8+ T lymphocyte depleted macaques. Monocyte expansion and kinetics in blood was assessed and newly migrated monocyte/macrophages were identified within the CNS. Five animals developed rapid AIDS with differing severity of SIVE. The percentages of BrdU+ monocytes in these animals increased dramatically, early after infection, peaking at necropsy where the percentage of BrdU+ monocytes correlated with the severity of SIVE. Early analysis revealed changes in the percentages of BrdU+ monocytes between slow and rapid progressors as early as 8 days and consistently by 27 days post infection. Soluble CD163 (sCD163) in plasma correlated with the percentage of BrdU+ monocytes in blood, demonstrating a relationship between monocyte activation and expansion with disease. BrdU+ monocytes/macrophages were found within perivascular spaces and SIVE lesions. The majority (80-90%) of the BrdU+ cells were Mac387+ that were not productively infected. There was a minor population of CD68+BrdU+ cells (<10%), very few of which were infected (<1% of total BrdU+ cells). Our results suggest that an increased rate of monocyte recruitment from bone marrow into the blood correlates with rapid progression to AIDS, and the magnitude of BrdU+ monocytes correlates with the severity of SIVE.
Insights
Increased monocyte recruitment from bone marrow correlates with rapid AIDS progression and simian immunodeficiency virus encephalitis (SIVE) severity in macaques. Newly identified monocytes contribute to central nervous system disease.
Area of Science:
- Immunology
- Virology
- Neuroscience
Background:
- Myeloid cells are key targets for human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV).
- Monocytes are crucial for immune responses during inflammation.
- Specific monocyte subsets may expand during AIDS, contributing to central nervous system (CNS) disease.
Purpose of the Study:
- To investigate the hypothesis that specific monocyte subsets expand during AIDS and drive CNS disease.
- To identify recently emigrated monocytes from bone marrow using 5-bromo-2'-deoxyuridine (BrdU) labeling.
- To assess monocyte kinetics and their role in SIV-induced pathogenesis.
Main Methods:
- Longitudinal study of SIV-infected, CD8+ T lymphocyte-depleted macaques.
- Utilized 5-bromo-2'-deoxyuridine (BrdU) labeling to track newly emigrated monocytes.
- Assessed monocyte expansion, kinetics in blood, and identified migrated monocyte/macrophages in the CNS.
Main Results:
- BrdU+ monocyte percentages increased dramatically in macaques with rapid AIDS progression, correlating with SIVE severity.
- Changes in BrdU+ monocyte percentages were observed early (8 days) and consistently (27 days) post-infection.
- Plasma soluble CD163 (sCD163) levels correlated with BrdU+ monocyte percentages, indicating a link between monocyte expansion and disease.
Conclusions:
- Increased monocyte recruitment from bone marrow into blood is associated with rapid AIDS progression.
- The expansion of BrdU+ monocytes correlates with the severity of SIVE.
- BrdU+ monocytes/macrophages accumulate in CNS perivascular spaces and SIVE lesions, with most not productively infected.
