RRC ID |
47791
|
著者 |
Nonaka S, Ando Y, Kanetani T, Hoshi C, Nakai Y, Nainu F, Nagaosa K, Shiratsuchi A, Nakanishi Y.
|
タイトル |
Signaling pathway for phagocyte priming upon encounter with apoptotic cells.
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ジャーナル |
J Biol Chem
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Abstract |
The phagocytic elimination of cells undergoing apoptosis is an evolutionarily conserved innate immune mechanism for eliminating unnecessary cells. Previous studies showed an increase in the level of engulfment receptors in phagocytes after the phagocytosis of apoptotic cells, which leads to the enhancement of their phagocytic activity. However, precise mechanisms underlying this phenomenon require further clarification. We found that the pre-incubation of a Drosophila phagocyte cell line with the fragments of apoptotic cells enhanced the subsequent phagocytosis of apoptotic cells, accompanied by an augmented expression of the engulfment receptors Draper and integrin αPS3. The DNA-binding activity of the transcription repressor Tailless was transiently raised in those phagocytes, depending on two partially overlapping signal-transduction pathways for the induction of phagocytosis as well as the occurrence of engulfment. The RNAi knockdown of tailless in phagocytes abrogated the enhancement of both phagocytosis and engulfment receptor expression. Furthermore, the hemocyte-specific RNAi of tailless reduced apoptotic cell clearance in Drosophila embryos. Taken together, we propose the following mechanism for the activation of Drosophila phagocytes after an encounter with apoptotic cells: two partially overlapping signal-transduction pathways for phagocytosis are initiated; transcription repressor Tailless is activated; expression of engulfment receptors is stimulated; and phagocytic activity is enhanced. This phenomenon most likely ensures the phagocytic elimination of apoptotic cells by stimulated phagocytes and is thus considered as a mechanism to prime phagocytes in innate immunity.
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巻・号 |
292(19)
|
ページ |
8059-8072
|
公開日 |
2017-5-12
|
DOI |
10.1074/jbc.M116.769745
|
PII |
S0021-9258(20)41899-X
|
PMID |
28325838
|
PMC |
PMC5427281
|
MeSH |
Animals
Apoptosis*
Cell Line
Cell Nucleus / metabolism
Cycloheximide / chemistry
Cytoskeletal Proteins / metabolism
DNA / analysis
Drosophila Proteins / metabolism
Drosophila melanogaster / metabolism
Hemocytes / cytology
Immunity, Innate
Integrin alpha Chains / metabolism
Membrane Proteins / metabolism
Oncogene Protein v-crk / metabolism
Phagocytes / cytology*
Phagocytosis
RNA Interference
Repressor Proteins / metabolism
Signal Transduction*
|
IF |
4.238
|
引用数 |
13
|
WOS 分野
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
リソース情報 |
ショウジョウバエ |
1762R-1 |