Up-regulation of phospholipase Cgamma1 and phospholipase D during the differentiation of human monocytes to dendritic cells.
Phospholipase C (PLC)gamma and phospholipase D (PLD) play pivotal roles in the signal transduction required for various cellular responses, including cell proliferation and differentiation. Dendritic cells (DCs), which are professional antigen-presenting cells, can be generated from human monocytes by stimulating the cells with granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin 4 (IL-4). We investigated whether PLCgamma and PLD expression levels can be changed during the differentiation of the human monocytes into DCs. The enzymatic activity and protein level of PLC gamma1 were significantly increased in the human monocyte-derived DCs by GM-CSF/IL-4, but the protein levels of PLC gamma2 were unaltered. Moreover, the enzymatic activity and protein level of PLD1b and PLD2 were up-regulated during the differentiation of human monocytes to DCs, but those of PLD1a were not changed. A higher phagocytic activity of DCs was found to be correlated with the up-regulations of PLCgamma1 and PLD, and the phagocytic activity of DCs was inhibited by a PLC-specific inhibitor (U73122) and by a phosphatidic acid acceptor (n-butanol), but to be increased by phosphatidic acid. Thus, suggesting that PLC and PLD participate in the process. This study suggests that the up-regulations of PLCgamma1 and PLD are accompanied by the differentiation of monocytes into DCs, which results in increased phagocytic activity.
Kang
Hyun Kyu
HK
Medical Research Center for Cancer Molecular Therapy, Dong-A University, Busan 602-714, South Korea.
Lee
Ha Young
HY
Lee
Youl-Nam
YN
Jo
Eun Jin
EJ
Kim
Jung Im
JI
Kim
Gi-Young
GY
Park
Yeong Min
YM
Min
Do Sik
DS
Yano
Akihiko
A
Kwak
Jong-Young
JY
Bae
Yoe-Sik
YS
D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects* / Q000201:enzymology; D020404:Glycerophospholipids / Q000096:biosynthesis; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D010587:Phagocytosis / Q000187:drug effects; D051966:Phospholipase C gamma; D010739:Phospholipase D / Q000096:biosynthesis* / Q000276:immunology; D015398:Signal Transduction; D010738:Type C Phospholipases / Q000096:biosynthesis* / Q000276:immunology; D015854:Up-Regulation
D020404:Glycerophospholipids; C068564:phosphatidylbutanol; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D010738:Type C Phospholipases; D051966:Phospholipase C gamma; D010739:Phospholipase D