Impaired responses of leukemic dendritic cells derived from a human myeloid cell line to LPS stimulation.
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 LPS- stimulated 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.
Kim
Kwang Dong
KD
Department of Biological Sciences, Sookmyung Women's University, Seoul 140-742, Korea.
Choi
Seung-Chul
SC
Noh
Young-Woock
YW
Kim
Jong Wan
JW
Paik
Sang-Gi
SG
Yang
Young
Y
Kim
Keun
K
Lim
Jong-Seok
JS
D018122:B7-1 Antigen / Q000378:metabolism; D051940:B7-2 Antigen / Q000378:metabolism; D015153:Blotting, Western; D019013:CD40 Antigens / Q000378:metabolism / Q000494:pharmacology; D023201:CD40 Ligand / Q000378:metabolism / Q000494:pharmacology; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000187:drug effects* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D016650:Fluorescein-5-isothiocyanate; D019084:Fluorescent Antibody Technique, Indirect; D005456:Fluorescent Dyes; D006801:Humans; D016753:Interleukin-10 / Q000032:analysis / Q000096:biosynthesis; D018664:Interleukin-12 / Q000032:analysis / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000378:metabolism; D007951:Leukemia, Myeloid / Q000473:pathology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D018122:B7-1 Antigen; D051940:B7-2 Antigen; D019013:CD40 Antigens; D005456:Fluorescent Dyes; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D023201:CD40 Ligand; D018664:Interleukin-12; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; D016650:Fluorescein-5-isothiocyanate