Diminished matrix metalloproteinase 9 secretion in human immunodeficiency virus-infected mononuclear phagocytes: modulation of innate immunity and implications for neurological disease.
Neurotoxic secretory products from virus-infected mononuclear phagocytes (MP; perivascular macrophages and microglia) orchestrate the neuropathogenesis of human immunodeficiency virus type one (HIV-1) infection. To uncover such MP products and their relationship to disease, we used a proteomics platform consisting of one dimensional polyacrylamide gel electrophoresis (1-DE), mass spectrometry peptide sequencing, and bioinformatics in order to identify from HIV-1-infected monocyte-derived macrophages (MDM) secretions. Matrix metalloproteinase 9 (MMP 9) secreted in abundance in MDM was markedly down-regulated following viral infection. A negative correlation between MMP 9 and HIV-1 reverse transcriptase activity was shown by quantitative Western blot assays. These data further demonstrate immunoregulatory activities of HIV-1-infected MDM providing unique insights into cellular function in disease.
Ciborowski
Pawel
P
Center for Neurovirology and Neurodegenerative Disorders, 985215 Nebraska Medical Center, University of Nebraska Medical Center, Omaha, NE 68198-5215, U SA. pcbirowski@unmc.edu
Enose
Yoshimi
Y
Mack
Andrea
A
Fladseth
Melissa
M
Gendelman
Howard E
HE
D015153:Blotting, Western / Q000379:methods; D019295:Computational Biology / Q000379:methods; D004591:Electrophoresis, Polyacrylamide Gel / Q000379:methods; D054303:HIV Reverse Transcriptase / Q000378:metabolism; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods; D020780:Matrix Metalloproteinase 9 / Q000032:analysis / Q000378:metabolism*; D010586:Phagocytes / Q000201:enzymology / Q000378:metabolism / Q000821:virology*; D020539:Sequence Analysis, Protein / Q000379:methods; D013997:Time Factors
D054303:HIV Reverse Transcriptase; D020780:Matrix Metalloproteinase 9