Induction of various immune modulatory molecules in CD34+ hematopoietic cells

Lipopolysaccharide (LPS) has been shown to induce proliferation of human T-lympho- cytes 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 im- munological 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-stimu- lated mononuclear cells (SUP LPS ) as well as tumor necrosis factor (NF-), but not LPS alone, can activate nuclear factor-B 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 B( IB)/IB (MAD-3), and intercellular ad- hesion 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-1 (MIP-1), MIP-1, RANTES, CD70, granulocyte macro- phage-colony stimulating factor, and IL-1 in stim- ulated KG-1a cells and CD34 BMCs. Although monokine induced by IFN-, IFN-inducible pro- tein 10, and IFN- 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- also showed enhanced secre- tion of MCP-1, MIP-1, MIP-1, and IL-8, and increased ICAM-1 protein expression could be de- tected in stimulated KG-1a cells and CD34 BMCs. Furthermore, we revealed that T cell pro- liferation can be induced by TNF--stimulated KG-1a cells, which is preventable by blocking anti- ICAM-1 monoclonal antibodies. Our results dem- onstrate that CD34 HCs have the potential to express a variety of immune-regulatory mediators upon stimulation by inflammatory cytokines in- cluding TNF-, which may contribute to innate- and adaptive-immune processes. J. Leukoc. Biol. 75: 671-679; 2004.