Exp Mol Med.  2006 Feb;38(1):72-84.

Impaired responses of leukemic dendritic cells derived from a human myeloid cell line to LPS stimulation

• Kim KD
• Choi SC
• Noh YW
• Kim JW
• Paik SG
• Yang Y
• Kim KI
• Lim JS

Abstract

Several myeloid leukemia-derived cells have been reported to possess the ability to differentiate into dendritic cells (DC). MUTZ-3, a myeloid leukemia cell line, responds to GM-CSF, IL-4 and TNF-alpha, and acquires a phenotype similar to immature monocyte-derived DC (MoDC). In the present study, MUTZ-3-derived DC (MuDC) showed high level expression of HLA class II molecules, CD80 and CD86, and were able to function as potent antigen presenting cells as previously reported. Interestingly, MuDC maturation was induced by CD40-mediated stimulation, but not by LPS stimulation. We analyzed CCR1, CCR7 and Toll-like receptor (TLR) expressions in MuDC, and measured IL-10 and IL-12 production after maturation stimuli. Although MuDC expressed the mRNA for TLR4, a major component of the LPS receptor system, they did not show an enhanced level of CCR7 or cytokine production after LPS stimulation. In contrast, they responded to CD40 stimulation, which resulted in increased levels of CD83, CD86 and CCR7. Moreover, while LPSstimulated MoDC could potently stimulate NK cells in a DC-NK cell co-culture, LPS-stimulated MuDC failed to stimulate primary NK cells. Taken together, our findings suggest that, although MuDC express TLR4, unlike TNF-alpha and IL-1beta, LPS does not stimulate MuDC to acquire mature phenotypes, and they may have impaired activity to initiate innate immune response.

Keyword

antigens; CD40; cell differentiation; dendritic cells; killer cells; natural; lipopolysaccharides; Toll-like receptors

MeSH Terms

Antigens, CD40/metabolism/pharmacology
Antigens, CD80/metabolism
Antigens, CD86/metabolism
Blotting, Western
CD40 Ligand/metabolism/pharmacology
Cell Differentiation
Cell Line, Tumor
Coculture Techniques
Dendritic Cells/*drug effects/metabolism
Enzyme-Linked Immunosorbent Assay
Fluorescein-5-isothiocyanate
Fluorescent Antibody Technique, Indirect
Fluorescent Dyes
Humans
Interleukin-10/analysis/biosynthesis
Interleukin-12/analysis/biosynthesis
Killer Cells, Natural/metabolism
Leukemia, Myeloid/*pathology
Lipopolysaccharides/*pharmacology
Mitogen-Activated Protein Kinase 3/metabolism
RNA, Messenger/metabolism
Research Support, Non-U.S. Gov't
Reverse Transcriptase Polymerase Chain Reaction
Toll-Like Receptor 4/metabolism
Tumor Necrosis Factor-alpha/pharmacology
p38 Mitogen-Activated Protein Kinases/metabolism