PMID- 14742640 OWN - NLM STAT- MEDLINE DCOM- 20040505 LR - 20081121 IS - 0741-5400 (Print) IS - 0741-5400 (Linking) VI - 75 IP - 4 DP - 2004 Apr TI - Induction of various immune modulatory molecules in CD34(+) hematopoietic cells. PG - 671-9 AB - 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. FAU - Umland, Oliver AU - Umland O AD - Department of Immunology and Cell Biology, Research Center Borstel, Borstel, Germany. FAU - Heine, Holger AU - Heine H FAU - Miehe, Michaela AU - Miehe M FAU - Marienfeld, Kathleen AU - Marienfeld K FAU - Staubach, Karl H AU - Staubach KH FAU - Ulmer, Artur J AU - Ulmer AJ LA - eng PT - Journal Article DEP - 20040123 PL - England TA - J Leukoc Biol JT - Journal of leukocyte biology JID - 8405628 RN - 0 (Adjuvants, Immunologic) RN - 0 (Antigens, CD34) RN - 0 (Chemokines) RN - 0 (Cytokines) RN - 0 (I-kappa B Proteins) RN - 0 (Inhibitor of Apoptosis Proteins) RN - 0 (Lipopolysaccharides) RN - 0 (Proteins) RN - 0 (Tumor Necrosis Factor-alpha) RN - 126547-89-5 (Intercellular Adhesion Molecule-1) SB - IM MH - Adjuvants, Immunologic/*metabolism MH - Antigens, CD34/biosynthesis/drug effects/*immunology MH - Cell Communication/drug effects/immunology MH - Cell Differentiation/drug effects/immunology MH - Cell Division/drug effects/immunology MH - Cell Line, Tumor MH - Chemokines/metabolism MH - Cytokines/drug effects/metabolism MH - Hematopoietic Stem Cells/drug effects/*immunology/metabolism MH - Humans MH - I-kappa B Proteins/drug effects/metabolism MH - Immunity, Innate/drug effects/*immunology MH - Inhibitor of Apoptosis Proteins MH - Intercellular Adhesion Molecule-1/drug effects/metabolism MH - Lipopolysaccharides/pharmacology MH - Lymphocyte Activation/drug effects/*immunology MH - Proteins/drug effects/metabolism MH - T-Lymphocytes/drug effects/*immunology/metabolism MH - Tumor Necrosis Factor-alpha/pharmacology MH - Up-Regulation/drug effects/immunology EDAT- 2004/01/27 05:00 MHDA- 2004/05/07 05:00 CRDT- 2004/01/27 05:00 PHST- 2004/01/27 05:00 [pubmed] PHST- 2004/05/07 05:00 [medline] PHST- 2004/01/27 05:00 [entrez] AID - jlb.1003501 [pii] AID - 10.1189/jlb.1003501 [doi] PST - ppublish SO - J Leukoc Biol. 2004 Apr;75(4):671-9. doi: 10.1189/jlb.1003501. Epub 2004 Jan 23.