Document Detail


Loss of macrophage-secreted lysozyme in HIV-1-associated dementia detected by SELDI-TOF mass spectrometry.
MedLine Citation:
PMID:  15096803     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: To identify which proteins are differentially secreted from monocyte/macrophages (M/M phi) of HIV-1 seropositive patients with HIV-1-associated dementia (HAD). DESIGN: To compare profiles of secreted M/M phi proteins from individuals with HAD, HIV-1 infection or controls using surface-enhanced laser desorption/ionization (SELDI)-time of flight (TOF) ProteinChip technology. METHODS: M/M phi were isolated by Percoll gradient centrifugation and cultured from whole blood of 11 patients with HAD, 13 HIV-1 seropositive subjects with no dementia (HIV-1 group) and nine HIV-1 seronegative subjects (controls). M/M phi supernatants were removed after 7 days in culture and analyzed by SELDI-TOF. A 14.6 kDa-secreted protein in control M/M phi supernatants was significantly decreased in patients with HAD. The protein was purified from HIV-1 seronegative controls and identified by peptide mapping. Protein concentration in the supernatants was quantified by enzyme-linked immunosorbent assay. RESULTS: A 14.6 kDa protein was identified as lysozyme. Secreted lysozyme concentrations from M/M phi of patients with HAD (81 +/- 35 ng/ml) were significantly lower than that of the HIV-1 group (326 +/- 303 ng/ml) and controls (764 +/- 211 ng/ml). Intracellular lysozyme was similar in all three groups. All patients with HAD were on highly active antiretroviral therapy (HAART). There was no correlation between lysozyme, viral load, CD4 cell count or use of HAART. CONCLUSIONS: A comparison of protein profiles from M/M phi supernatants of patients with HIV-1 infection indicated a specific protein consistently decreased in HAD. The protein was identified as lysozyme, a major macrophage defense protein. This further demonstrates macrophage dysfunction as a significant consequence of HAD.
Authors:
Bing Sun; Hans C Rempel; Lynn Pulliam
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  AIDS (London, England)     Volume:  18     ISSN:  0269-9370     ISO Abbreviation:  AIDS     Publication Date:  2004 Apr 
Date Detail:
Created Date:  2004-04-20     Completed Date:  2004-08-03     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  8710219     Medline TA:  AIDS     Country:  England    
Other Details:
Languages:  eng     Pagination:  1009-12     Citation Subset:  IM; X    
Affiliation:
Department of Laboratory Medicine, University of California, and Veterans Affairs Medical Center, San Francisco, USA.
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MeSH Terms
Descriptor/Qualifier:
AIDS Dementia Complex / drug therapy,  enzymology*,  virology
Antiretroviral Therapy, Highly Active
Biological Markers / blood
CD4 Lymphocyte Count
HIV Infections / drug therapy,  enzymology,  virology
HIV-1*
Humans
Macrophages / enzymology*
Muramidase / blood*
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / methods
Viral Load
Grant Support
ID/Acronym/Agency:
R21MH064406/MH/NIMH NIH HHS
Chemical
Reg. No./Substance:
0/Biological Markers; EC 3.2.1.17/Muramidase

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