The anti-inflammatory role of apoptotic ATRA-NB4 cells in the resolution of differentiation syndrome

碩士 === 國立陽明大學 === 生理學研究所 === 100 === All- trans retinoic acid (ATRA) has been used successfully in the treatment of acute promyelocytic leukemia (APL). However, this treatment may complicate with differentiation syndrome (DS) in 30% of patients, which manifests with clinical picture of acute lung in...

Full description

Bibliographic Details
Main Authors: I-Ting Li, 李伊婷
Other Authors: Hui-Chi Hsu
Format: Others
Language:zh-TW
Published: 2012
Online Access:http://ndltd.ncl.edu.tw/handle/12833815224409163853
id ndltd-TW-100YM005116025
record_format oai_dc
spelling ndltd-TW-100YM0051160252015-10-13T21:22:40Z http://ndltd.ncl.edu.tw/handle/12833815224409163853 The anti-inflammatory role of apoptotic ATRA-NB4 cells in the resolution of differentiation syndrome 凋亡之經全反式維甲酸治療的前骨髓性白血病細胞在發炎恢復期與抗發炎的角色 I-Ting Li 李伊婷 碩士 國立陽明大學 生理學研究所 100 All- trans retinoic acid (ATRA) has been used successfully in the treatment of acute promyelocytic leukemia (APL). However, this treatment may complicate with differentiation syndrome (DS) in 30% of patients, which manifests with clinical picture of acute lung injury and massive infiltration of ATRA-treated APL (ATRA-APL) cells into alveolar spaces. It is not clear how these ATRA-APL cells were cleared during resolution phase of DS. Previous studies have reported that cross-talk between apoptotic ATRA-APL cells and alveolar macrophage is crucial during the resolution phase of DS. In this study, we investigated the mechanism underlying the interaction between apoptotic ATRA-APL (NB4) cells and alveolar macrophages (NR8383). Different stages of apoptotic cells were determined by flowcytometry by using antibodies specific to annexin V and 7-AAD. Condition medium (CM) derived from apoptotic ATRA-NB4 cells was harvested to determine its biological activity by transmigration assay and adhesion assay. Our results indicated that NR8383 cells were able to engulf apoptotic ATRA-NB4 cells. Furthermore, the CM derived from apoptotic ATRA-NB4 cells had anti-inflammatory activity as evidenced by inhibiting the recipient cells migration and adhesion to human umbilical vein endothelial cells (HUVEC). Further studies we focused on investigating the mediators responsible for the anti-inflammatory activities in the CM which facilitate the phagocytosis activity of alveolar macrophage. Annexin A1 is a mediator that regulates the immune response of glucocorticoids. We found that apoptotic ATRA-NB4 cells would release Annexin A1 via microparticle (MP). On the other hand, the release of the pro-inflammatory cytokine: IL-8 will diminish as well. Based on these finding, we conclude that the CM collected from apoptotic ATRA-NB4 cells has anti-inflammatory activities by releasing AnxA1(+) MP and reducing the release of IL-8. During the resolution stage of DS, these apoptotic cells could increase clearance of dying cells and prevent further infiltration in alveolar. Thus, these findings would suggest the potential therapeutic strategies to modulate the resolution of acute lung injury in DS. Hui-Chi Hsu 徐會棋 2012 學位論文 ; thesis 73 zh-TW
collection NDLTD
language zh-TW
format Others
sources NDLTD
description 碩士 === 國立陽明大學 === 生理學研究所 === 100 === All- trans retinoic acid (ATRA) has been used successfully in the treatment of acute promyelocytic leukemia (APL). However, this treatment may complicate with differentiation syndrome (DS) in 30% of patients, which manifests with clinical picture of acute lung injury and massive infiltration of ATRA-treated APL (ATRA-APL) cells into alveolar spaces. It is not clear how these ATRA-APL cells were cleared during resolution phase of DS. Previous studies have reported that cross-talk between apoptotic ATRA-APL cells and alveolar macrophage is crucial during the resolution phase of DS. In this study, we investigated the mechanism underlying the interaction between apoptotic ATRA-APL (NB4) cells and alveolar macrophages (NR8383). Different stages of apoptotic cells were determined by flowcytometry by using antibodies specific to annexin V and 7-AAD. Condition medium (CM) derived from apoptotic ATRA-NB4 cells was harvested to determine its biological activity by transmigration assay and adhesion assay. Our results indicated that NR8383 cells were able to engulf apoptotic ATRA-NB4 cells. Furthermore, the CM derived from apoptotic ATRA-NB4 cells had anti-inflammatory activity as evidenced by inhibiting the recipient cells migration and adhesion to human umbilical vein endothelial cells (HUVEC). Further studies we focused on investigating the mediators responsible for the anti-inflammatory activities in the CM which facilitate the phagocytosis activity of alveolar macrophage. Annexin A1 is a mediator that regulates the immune response of glucocorticoids. We found that apoptotic ATRA-NB4 cells would release Annexin A1 via microparticle (MP). On the other hand, the release of the pro-inflammatory cytokine: IL-8 will diminish as well. Based on these finding, we conclude that the CM collected from apoptotic ATRA-NB4 cells has anti-inflammatory activities by releasing AnxA1(+) MP and reducing the release of IL-8. During the resolution stage of DS, these apoptotic cells could increase clearance of dying cells and prevent further infiltration in alveolar. Thus, these findings would suggest the potential therapeutic strategies to modulate the resolution of acute lung injury in DS.
author2 Hui-Chi Hsu
author_facet Hui-Chi Hsu
I-Ting Li
李伊婷
author I-Ting Li
李伊婷
spellingShingle I-Ting Li
李伊婷
The anti-inflammatory role of apoptotic ATRA-NB4 cells in the resolution of differentiation syndrome
author_sort I-Ting Li
title The anti-inflammatory role of apoptotic ATRA-NB4 cells in the resolution of differentiation syndrome
title_short The anti-inflammatory role of apoptotic ATRA-NB4 cells in the resolution of differentiation syndrome
title_full The anti-inflammatory role of apoptotic ATRA-NB4 cells in the resolution of differentiation syndrome
title_fullStr The anti-inflammatory role of apoptotic ATRA-NB4 cells in the resolution of differentiation syndrome
title_full_unstemmed The anti-inflammatory role of apoptotic ATRA-NB4 cells in the resolution of differentiation syndrome
title_sort anti-inflammatory role of apoptotic atra-nb4 cells in the resolution of differentiation syndrome
publishDate 2012
url http://ndltd.ncl.edu.tw/handle/12833815224409163853
work_keys_str_mv AT itingli theantiinflammatoryroleofapoptoticatranb4cellsintheresolutionofdifferentiationsyndrome
AT lǐyītíng theantiinflammatoryroleofapoptoticatranb4cellsintheresolutionofdifferentiationsyndrome
AT itingli diāowángzhījīngquánfǎnshìwéijiǎsuānzhìliáodeqiángǔsuǐxìngbáixuèbìngxìbāozàifāyánhuīfùqīyǔkàngfāyándejiǎosè
AT lǐyītíng diāowángzhījīngquánfǎnshìwéijiǎsuānzhìliáodeqiángǔsuǐxìngbáixuèbìngxìbāozàifāyánhuīfùqīyǔkàngfāyándejiǎosè
AT itingli antiinflammatoryroleofapoptoticatranb4cellsintheresolutionofdifferentiationsyndrome
AT lǐyītíng antiinflammatoryroleofapoptoticatranb4cellsintheresolutionofdifferentiationsyndrome
_version_ 1718062924093718528