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Induction of various immune modulatory molecules in CD34 + hematopoietic cells
Author(s) -
Umland Oliver,
Heine Holger,
Miehe Michaela,
Marienfeld Kathleen,
Staubach Karl H.,
Ulmer Artur J.
Publication year - 2004
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.1003501
Subject(s) - biology , haematopoiesis , cd34 , chemokine , microbiology and biotechnology , monocyte , tumor necrosis factor alpha , macrophage inflammatory protein , interleukin 3 , progenitor cell , myeloid , immunology , immune system , cancer research , stem cell , t cell , antigen presenting cell
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 α (ΤNF‐α), but not LPS alone, can activate nuclear factor‐κB 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 κB (IκB)/IκBα (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‐1α (MIP‐1α), MIP‐1β, RANTES, CD70, granulocyte macrophage‐colony stimulating factor, and IL‐1β in stimulated KG‐1a cells and CD34 + BMCs. Although monokine induced by IFN‐γ, IFN‐inducible protein 10, and IFN‐γ 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‐α also showed enhanced secretion of MCP‐1, MIP‐1α, MIP‐1β, 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‐α‐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‐α, which may contribute to innate‐ and adaptive‐immune processes.