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YKL-40, a marker of simian immunodeficiency virus encephalitis, modulates the biological activity of basic fibroblast growth factor.
- Source :
-
The American journal of pathology [Am J Pathol] 2008 Jul; Vol. 173 (1), pp. 130-43. Date of Electronic Publication: 2008 Jun 13. - Publication Year :
- 2008
-
Abstract
- Human immunodeficiency virus encephalitis causes dementia in acquired immune deficiency syndrome patients. Using proteomic analysis of postmortem cerebrospinal fluid (CSF) and brain tissue from the simian immunodeficiency virus primate model, we demonstrate here a specific increase in YKL-40 that was tightly associated with lentiviral encephalitis. Longitudinal analysis of CSF from simian immunodeficiency virus-infected pigtailed macaques showed an increase in YKL-40 concentration 2 to 8 weeks before death from encephalitis. This increase in YKL-40 correlated with an increase in CSF viral load; it may therefore represent a biomarker for the development of encephalitis. Analysis of banked human CSF from human immunodeficiency virus-infected patients also demonstrated a correlation between YKL-40 concentration and CSF viral load. In vitro studies demonstrated increased YKL-40 expression and secretion by macrophages and microglia but not by neurons or astrocytes. We found that YKL40 displaced extracellular matrix-bound basic fibroblast growth factor (bFGF) as well as inhibited the mitogenic activity of both fibroblast growth factor receptor 1-expressing BaF3 cells and bFGF-induced axonal branching in hippocampal cultures. Taken together, these findings demonstrate that during lentiviral encephalitis, YKL-40 may interfere with the biological activity of bFGF and potentially of other heparin-binding growth factors and chemokines that can affect neuronal function or survival.
- Subjects :
- Adipokines
Animals
Blotting, Western
Chitinase-3-Like Protein 1
Encephalitis, Viral metabolism
Enzyme-Linked Immunosorbent Assay
Extracellular Matrix
Glycoproteins
HIV Infections complications
HIV Infections metabolism
Humans
Immunohistochemistry
In Situ Hybridization
Lectins
Macaca nemestrina
Mass Spectrometry
Microglia metabolism
Reverse Transcriptase Polymerase Chain Reaction
Simian Acquired Immunodeficiency Syndrome complications
Simian Acquired Immunodeficiency Syndrome metabolism
Simian Immunodeficiency Virus
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Biomarkers cerebrospinal fluid
Encephalitis, Viral cerebrospinal fluid
Fibroblast Growth Factor 2 metabolism
Simian Acquired Immunodeficiency Syndrome cerebrospinal fluid
Subjects
Details
- Language :
- English
- ISSN :
- 1525-2191
- Volume :
- 173
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- The American journal of pathology
- Publication Type :
- Academic Journal
- Accession number :
- 18556781
- Full Text :
- https://doi.org/10.2353/ajpath.2008.080045