2003 Fiscal Year Final Research Report Summary
A STUDY ON MECHANISMS OF NEUTROPHIL APOPTOSIS IN RAT CARRAGEENIN-INDUCED PLEURISY
| Project/Area Number |
13670095
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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 |
General pharmacology
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| Research Institution | Kitasato University |
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Principal Investigator |
HARADA Yoshiteru KITASATO UNIVERSITY SCHOOL OF ALLIED MEDICAL SCIENCES, DEPARTMENT OF PHARMACOLOGY, PROFESSOR, 医療衛生学部, 教授 (20050677)
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| Project Period (FY) |
2001 – 2003
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| Keywords | NEUTROPHIL APOPTOSIS / INFLAMMATION / MACROPHAGES / CYCLOOXYGENASE / NITRlC OXIDE / LYMPH NODES / CARRAGEENIN / PLEURISY |
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| Research Abstract |
Granulocyte apoptosis and subsequent clearance by phagocytes is critical for the resolution of inflammation. However, no studies have addressed how the resolution proceed in the inflammatory site. We studied the time course of neutrophil apoptosis and the following ingestion by mononuclear leukocytes in rat carrageenin-induced pleurisy, detecting DNA fragmentation by the TUNEL method, by acridine orange staining and from the DNA ladder pattern on electrophoresis. Neutrophil accumulation started 3-5 hrs after carrageenin injection, then maintained a plateau until 24 hr. Neutrophils decreased steeply between days 1 and 3. Mononuclear leukocytes started to accumulate at 5 hr, and reached a peak at day 2. TUNEL-positive bodies and acridine orange-positive bodies first became detectable in the cytoplasm of the mononuclear leukocytes from 24 hr and 9 hr, respectively. Both methods indicated that mononuclear leukocytes containing fragmented DNA increased rapidly on days 1 and 2, and reached a peak at day 3. The characteristic ladder pattern of neutrophil DNA was observed from 5 hr. Furthermore, an apoptosis related protein, Bad, became detectable in the exudate leukocytes from 9 hr after carrageenin injection. These results indicate that neutrophils start to undergo apoptosis just after the beginning of their accumulation in the inflammation site. Thus, evolution and resolution processes may proceed concurrently in acute inflammation.
Parathymic lymph nodes enlarged with progression of inflammation. A large number of neutrophils and mononuclear leukocytes increasingly appeared in the enlarged lymph nodes. These cells expressed inducible nitric oxide synthase. In addition, cells possessing dendritic processes in the enlarged lymph nodes expressed cyclooxygenase-2. These results suggest that a part of neutrophils transmigrate into adjacent draining lymph nodes.
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[Publications] Hatanaka, K., Kawamura, M., Murai, N., Ogino, M., Majima, M., Ogino, K., Harada, Y.: "FR 167653, a cytokine synthesis inhibitor, exhibits anti-inflammatory effects early in rat carrageenin-induced pleurisy but no effect later."J.Pharmacol.ExThera. 299(2). 519-527 (2001)
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「研究成果報告書概要(欧文)」より
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[Publications] Murai, N., Nagai, K., Fujisawa, H., Hatanaka, K., Kawamura, M., Harada, Y.: "Concurrent evolution and resolution in an acute inflammatory model of rat carrageenin-induced pleurisy."J.Leukoc.Biol.. 73(4). 456-463 (2003)
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「研究成果報告書概要(欧文)」より
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[Publications] Fujisawa, H., Nakagawa, S., Ohkubo, Y., Matsui, M., Yamaguchi, S., Kawamura, M., Hatanaka, K., Kawakubo, Y., Hiramoto, Y., Kobayashi, H., Harada Y.: "Characterization of expression of inducible nitric oxide synthase in comparison with that of cyclooxygenase-2 in rat carrageenin-induced pleurisy."(in submission).
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「研究成果報告書概要(欧文)」より
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[Publications] Kawamura, M., Hatanaka, K., Murai, N., Majima, M., Ogino, K., Harada Y.: "Effects of a cytokine suppressive agent ; FR 176653, on the early and late phases of the rat carrageenin-induced pleurisy."Jpn.J.Pharmacol.. 85(Suppl I). 121 (2001)
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「研究成果報告書概要(欧文)」より
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