title: HIV type 1 protease inhibitors enhance bone marrow progenitor cell activity in normal subjects and in HIV type 1-infected patients.
abstract: HIV-1 protease inhibitors (PIs) may improve hematopoietic functions owing to their direct effects on bone marrow (BM) progenitor cells. In this study we investigated this hypothesis evaluating the effect of adding ritonavir (RTV) and indinavir (IND) on hematopoietic colony formation assays by colony-forming cell (CFC) and long-term culture-initiating cell (LTC-IC) assays, on apoptosis, on cytokine production and stromal cells, in subjects with HIV-1 infection, and in seronegative controls. After PI addition, CFC and LTC-IC assays in HIV-1-infected patients showed levels of colony growth significantly higher than those observed at baseline; the same PI activity on colony formation was observed in healthy subjects. No significant modifications on Fas, the membrane form of Fas (mFas) and Fas-ligand (FasL) expression, and on cytokine production were observed at BM level after the addition of PIs. At baseline, in HIV-1-infected patients, the majority of the stromal cells appeared as large and rounded, whereas after the addition of RTV or IND the stromal cells exhibited a "fibroblast-like" morphology and produced higher stem cell factor (SCF) and lower MIP-1alpha levels when compared with the stromal production without the addition of IND. RTV and IND increased colony growth of BM obtained either from HIV-1-infected patients or from normal individuals, in parallel with the normalization of functional and morphological characteristics of stromal cells.
authors.affiliation: Division of Allergy and Clinical Immunology, University of Rome "La Sapienza," 00185 Rome, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Isgrò
authors.forename: Alessandro
authors.initials: A
authors.lastname: Aiuti
authors.forename: Ivano
authors.initials: I
authors.lastname: Mezzaroma
authors.forename: Luigi
authors.initials: L
authors.lastname: Ruco
authors.forename: Marcello
authors.initials: M
authors.lastname: Pinti
authors.forename: Andrea
authors.initials: A
authors.lastname: Cossarizza
authors.forename: Fernando
authors.initials: F
authors.lastname: Aiuti
mesh_terms: D000328:Adult; D017209:Apoptosis; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects*; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D005260:Female; D015658:HIV Infections; D017320:HIV Protease Inhibitors / Q000494:pharmacology*; D018023:HIV Seronegativity; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D019469:Indinavir / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D019438:Ritonavir / Q000494:pharmacology*; D017154:Stromal Cells
chemical_list: D016207:Cytokines; D017320:HIV Protease Inhibitors; D019469:Indinavir; D019438:Ritonavir