Ancuta P, Rao R, Moses A, Mehle A, Wurcel A, Stone D, Luscinskas FW, Gabuzda D; Conference on Retroviruses and Opportunistic Infections.
Abstr 10th Conf Retrovir Oppor Infect Feb 10 14 2003 Hynes Conv Cent Boston Mass USA Conf Retrovir Oppor Infect 10th 2003 Boston Mass. 2003 Feb 10-14; 10: abstract no. 684.
Dana-Farber Cancer Inst, Boston, MA
BACKGROUND: The percentage of circulating CD16+ monocytes (Mo) is dramatically increased in patients (pts) with HIV-associated dementia (HAD). Furthermore, perivascular CD16+ monocytes/macrophages are a major reservoir of virus in the CNS. In this study, we investigated mechanisms of CD16+ Mo trafficking that may increase HIV entry into the brain and contribute to neurologic injury in HAD.METHODS: PBMC isolated from fresh blood of HIV- individuals and HAD patients (pts) were triple stained with anti-CD14, anti-CD16, and a large panel of mAbs and analyzed by FACS to phenotypically characterize Mo subsets. Total Mo isolated by negative selection were stained with anti-CD16, and CD16-/CD16+ Mo subsets were assessed for their ability to undergo transwell/transendothelial migration in response to MCP-1, MIP-1a, SDF-1a, and FKN and firm adhesion to TNF-a/IFN-g-stimulated or FKN-expressing endothelial cells (EC) under flow conditions. CD16-/CD16+ Mo isolated by negative/positive selection were co-cultured with resting, TNF-a/IFN-g-stimulated or FKN-expressing EC for 48 h and MMP-9 levels in the supernatants were detected by ELISA.RESULTS: In HIV- individuals, CD16+ Mo express high CX3CR1 and CXCR4 and low CCR1 and CCR2 levels, and migrate in response to FKN and SDF-1a but not MIP-1a and MCP-1. Despite low expression of CD62L, CD16+ Mo undergo firm arrest on TNF-a/IFN-g-stimulated or FKN-expressing EC under flow conditions. CD16+ Mo, but not CD16- Mo, produce high MMP-9 levels when co-cultured with TNF-a/IFN-g stimulated or FKN-expressing EC. In HAD pts, the expression of CCR1, CCR2, CXCR4, and CX3CR1 on CD16+ Mo was similar to that detected in HIV- individuals. However, we found a significantly lower expression of CCR1, CCR2, and CD62L on CD16- Mo in HAD pts compared to HIV- individuals.CONCLUSIONS: These results suggest that FKN and SDF-1a play an important role in recruitment of CD16+ Mo into peripheral tissues. This finding together with previous studies which showed increased expression of FKN and SDF-1a in the CNS of HAD pts suggest that CD16+ Mo can migrate into the CNS and contribute to neurologic injury in HAD. The high levels of MMP-9 produced by CD16+ Mo after interaction with EC may affect the integrity of the blood-brain barrier, particularly in HAD pts where the number of circulating CD16+ Mo is dramatically increased.
Publication Types:
Keywords:
- AIDS Dementia Complex
- Acquired Immunodeficiency Syndrome
- Antigens, CD14
- Brain
- CX3CR1 protein, human
- Cell Movement
- FCGR3B protein, human
- HIV
- HIV Seropositivity
- HIV-1
- Humans
- Interferon Type II
- Matrix Metalloproteinase 9
- Monocytes
- Protein Transport
- Receptors, Chemokine
- Receptors, HIV
- Receptors, IgG
- immunology
Other ID:
UI: 102261318
From Meeting Abstracts