title: Induction of various immune modulatory molecules in CD34(+) hematopoietic cells.
abstract: Lipopolysaccharide (LPS) has been shown to induce proliferation of human T-lymphocytes only in the presence of monocytes and CD34(+) hematopoietic cells (HCs) from peripheral blood. This finding provided evidence of an active role of CD34(+) HCs during inflammation and immunological events. To investigate mechanisms by which CD34(+) HCs become activated and exert their immune-modulatory function, we used the human CD34(+) acute myeloid leukemia cell line KG-1a and CD34(+) bone marrow cells (BMCs). We showed that culture supernatants of LPS-stimulated mononuclear cells (SUP(LPS)) as well as tumor necrosis factor alpha (TauNF-alpha), but not LPS alone, can activate nuclear factor-kappaB in KG-1a cells. By cDNA subtraction and multiplex polymerase chain reaction, we revealed differential expression of cellular inhibitor of apoptosis protein-1, inhibitor of kappaB (IkappaB)/IkappaBalpha (MAD-3), and intercellular adhesion molecule-1 (ICAM-1) in SUP(LPS)-stimulated KG-1a cells and up-regulation of interferon (IFN)-inducible T cell-chemoattractant, interleukin (IL)-8, macrophage-inflammatory protein-1alpha (MIP-1alpha), MIP-1beta, RANTES, CD70, granulocyte macrophage-colony stimulating factor, and IL-1beta in stimulated KG-1a cells and CD34(+) BMCs. Although monokine induced by IFN-gamma, IFN-inducible protein 10, and IFN-gamma were exclusively up-regulated in KG-1a cells, differential expression of monocyte chemoattractant protein-1 (MCP-1), macrophage-derived chemokine, myeloid progenitor inhibitory factor-2, and IL-18 receptor was only detectable in CD34(+) BMCs. More importantly, CD34(+) BMCs stimulated by TNF-alpha also showed enhanced secretion of MCP-1, MIP-1alpha, MIP-1beta, and IL-8, and increased ICAM-1 protein expression could be detected in stimulated KG-1a cells and CD34(+) BMCs. Furthermore, we revealed that T cell proliferation can be induced by TNF-alpha-stimulated KG-1a cells, which is preventable by blocking anti-ICAM-1 monoclonal antibodies. Our results demonstrate that CD34(+) HCs have the potential to express a variety of immune-regulatory mediators upon stimulation by inflammatory cytokines including TNF-alpha, which may contribute to innate- and adaptive-immune processes.
authors.affiliation: Department of Immunology and Cell Biology, Research Center Borstel, Borstel, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Umland
authors.forename: Holger
authors.initials: H
authors.lastname: Heine
authors.forename: Michaela
authors.initials: M
authors.lastname: Miehe
authors.forename: Kathleen
authors.initials: K
authors.lastname: Marienfeld
authors.forename: Karl H
authors.initials: KH
authors.lastname: Staubach
authors.forename: Artur J
authors.initials: AJ
authors.lastname: Ulmer
mesh_terms: D000276:Adjuvants, Immunologic / Q000378:metabolism*; D018952:Antigens, CD34 / Q000096:biosynthesis / Q000187:drug effects / Q000276:immunology*; D002450:Cell Communication / Q000187:drug effects / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D045744:Cell Line, Tumor; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D020672:I-kappa B Proteins / Q000187:drug effects / Q000378:metabolism; D007113:Immunity, Innate / Q000187:drug effects / Q000276:immunology*; D051034:Inhibitor of Apoptosis Proteins; D018799:Intercellular Adhesion Molecule-1 / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D011506:Proteins / Q000187:drug effects / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D018952:Antigens, CD34; D018925:Chemokines; D016207:Cytokines; D020672:I-kappa B Proteins; D051034:Inhibitor of Apoptosis Proteins; D008070:Lipopolysaccharides; D011506:Proteins; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1