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. (C) 2004 Elsevier B.V. All rights reserved.