title: Investigating the human immunodeficiency virus type 1-infected monocyte-derived macrophage secretome.
abstract: Mononuclear phagocytes (bone marrow monocyte-derived macrophages, alveolar macrophages, perivascular macrophages, and microglia) are reservoirs and vehicles of dissemination for the human immunodeficiency virus type-1 (HIV-1). How virus alters mononuclear phagocyte immunoregulatory activities to complete its life cycle and influence disease is incompletely understood. In attempts to better understanding the influence of virus on macrophage functions, we used one-dimensional electrophoresis, and liquid chromatography tandem mass spectrometry to analyze the secretome of HIV-1-infected human monocyte-derived macrophages. We identified 110 proteins in culture supernatants of control (uninfected) and virus-infected cells. Differentially expressed cytoskeletal, enzymes, redox, and immunoregulatory protein classes were discovered and validated by Western blot tests. These included, but were not limited to, cystatin C, cystatin B, chitinase 3-like 1 protein, cofilin-1, l-plastin, superoxide dismutase, leukotriene A(4) hydrolase, and alpha-enolase. This study, using a unique proteomics platform, provides novel insights into virus-host cell interactions that likely affect the functional role of macrophages in HIV disease.
authors.affiliation: Center for Neurovirology and Neurodegenerative Disorders, University of Nebraska Medical Center, Omaha, NE 68198-5800, USA. pciborowski@unmc.edu
authors.forename: Pawel
authors.initials: P
authors.lastname: Ciborowski
authors.forename: Irena
authors.initials: I
authors.lastname: Kadiu
authors.forename: Wojciech
authors.initials: W
authors.lastname: Rozek
authors.forename: Lynette
authors.initials: L
authors.lastname: Smith
authors.forename: Kristen
authors.initials: K
authors.lastname: Bernhardt
authors.forename: Melissa
authors.initials: M
authors.lastname: Fladseth
authors.forename: Mary
authors.initials: M
authors.lastname: Ricardo-Dukelow
authors.forename: Howard E
authors.initials: HE
authors.lastname: Gendelman
mesh_terms: D015153:Blotting, Western; D002478:Cells, Cultured; D004591:Electrophoresis, Polyacrylamide Gel; D005786:Gene Expression Regulation; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology / Q000821:virology*; D009000:Monocytes / Q000166:cytology*; D011506:Proteins / Q000032:analysis* / Q000378:metabolism*; D021241:Spectrometry, Mass, Electrospray Ionization; D013997:Time Factors
chemical_list: D011506:Proteins