Conant K, Irani D, Sjulson L, Griffin DE, McArthur JC; Conference on Retroviruses and Opportunistic Infections.
Program Abstr 6th Conf Retrovir Oppor Infect Conf Retrovir Oppor Infect 6th 1999 Chic Ill. 1999 Jan 31-Feb 4; 6th: 121 (abstract no. 282).
Johns Hopkins University, Baltimore, MD.
Pathological evidence suggests that alterations of the blood brain barrier (BBB) occur in association with HIV dementia. Increased BBB permeability could contribute to the development of this condition by facilitating the entry of activated and/or HIV infected monocytes, as well as potentially toxic serum proteins, into the central nervous system (CNS). In the present study, we examined the possibility that select matrix metalloproteinases (MMPs), which target critical BBB proteins including collagen type IV, are elevated in HIV dementia. We also studied whether the production of these MMPs, by both monocytes and brain derived cells, might be increased in response to stimulation with gp120 and/or TNF-alpha. Using Western blot and ELISA to analyse cerebrospinal fluid samples from clinically characterized individuals, we observed that the pro forms of both MMP-2 and -7 are increased in HIV dementia. In addition, through the use of gelatin substrate zymography, a functional assay for MMP-2 and -9, we observed that while MMP-2 activity was detectable in all tested individuals, MMP-9 activity was more frequently detected in those with HIV dementia than in those without (3/10 seronegative individuals, 6/12 HIV infected without dementia and 10/16 with HIV dementia). Moreover, consistent with these observations, we observed that monocytes and microglial cells produce MMP-7 and -9, and that such production is increased following their stimulation with either TNF-alpha or gp120. Together, these results suggest that excessive production of MMPs which target BBB proteins may play a role in the development of HIV dementia.
Publication Types:
Keywords:
- AIDS Dementia Complex
- Acquired Immunodeficiency Syndrome
- Blood-Brain Barrier
- Blotting, Western
- Brain
- Enzyme-Linked Immunosorbent Assay
- HIV Envelope Protein gp120
- HIV Infections
- HIV Seropositivity
- Human Development
- Matrix Metalloproteinase 2
- Matrix Metalloproteinase 7
- Matrix Metalloproteinases
- Microglia
- Monocytes
- growth & development
- immunology
Other ID:
UI: 102188924
From Meeting Abstracts