1999 Fiscal Year Final Research Report Summary
Regulation mechanism of phagocytotic process in leukocytes by an actin-binding protein, p57, and immune diseases
| Project/Area Number |
10672064
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | Hoshi University |
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Principal Investigator |
TOYOSHIMA Satoshi Hosei University, Faculty of Pharmaceutical Science, Professor, 薬学部, 教授 (40092283)
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| Project Period (FY) |
1998 – 1999
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| Keywords | actin-binding protein, p57 / leukocytes / phagocytes / phagosome / acin / NADPH osidase / Protein kinase C / X-linked chronic granulomatous disease |
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| Research Abstract |
In the present study, intracellular translocation of the actin-binding protein, p57, in phagocytotic leukocytes and its mechanism were investigated. First, two anitbodies with defferent specificities were prepared for the detection of intracellular p57. Ingestion of opsonized zymosan (OpZ) in neutrophils began within 30 seconds of particle binding and forming phagosomes were enriched for both F-action and p57. However, F-actin and p57 were shed from nascent phagosomes once particle internalization was complete (【approximately equal】5 MINUTES). On the other hand, NADPH oxidase subunits p47phox and p67phox were also recruited to forming phagosomes and were retained on mature phagosomes for at least 15 minutes. These results suggest that p57 plays some role in the formation of phagosomes but not in the expression of mature phagosome function such as superoxide generation. Then, the mechanism of p57 shedding from phagosomes was investigated. Since it has been shown that protein phosphorylation plays a key role in the signaling pathway duraing phagocytosis, phosphorylation of p57 during phagocytosis was studies. Ingestion of OpZ induced a transient increase of p57 phosphorylation. The time of increased phosphorylation corresponded with that of p57 shedding from phagosome. To investigate which protein kinase is responsible for the shedding, effects of inhibitors of protein phosphorylation on it was studied. It was found that protein kinase C inhibitors suppressed the p57 shedding.
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