1. Kor /
  2. Eng

  1. Kor /
  2. Eng

Major AchievementsFollowings are the major outstanding achievements of the SAIHST faculties

[배외식 교수] 패혈증 치료를 위한 표적분자 규명 및 신약물질 발견
No 4
Date 2015/12/07

 

     
 SCI IF= 13.912               배외식 교수                              

 (2013년도기준) (자연대 생명과학/SAIHST겸직)

                                        ★ 책임저자            

 

 

2015 Aug 24;212(9):1381-90. doi: 10.1084/jem.20141813. Epub 2015 Aug 17.

Phospholipase D2 drives mortality in sepsis by inhibiting neutrophil extracellular trap formation and down-regulating CXCR2.

 

Abstract

We determined the function of phospholipase D2 (PLD2) in host defense in highly lethal mouse models of sepsis using PLD2(-/-) mice and a PLD2-specific inhibitor. PLD2 deficiency not only increases survival but also decreases vital organ damage during experimental sepsis. Production of several inflammatory cytokines (TNF, IL-1β, IL-17, and IL-23) and the chemokine CXCL1, as well as cellular apoptosis in immune tissues, kidney, and liver, are markedly decreased in PLD2(-/-) mice. Bactericidal activity is significantly increased in PLD2(-/-) mice, which is mediated by increased neutrophil extracellular trap formation and citrullination of histone 3 through peptidylarginine deiminase activation. Recruitment of neutrophils to the lung is markedly increased in PLD2(-/-) mice. Furthermore, LPS-induced induction of G protein-coupled receptor kinase 2 (GRK2) and down-regulation of CXCR2 are markedly attenuated in PLD2(-/-) mice. A CXCR2-selective antagonist abolishes the protection conferred by PLD2 deficiency during experimental sepsis, suggesting that enhanced CXCR2 expression, likely driven by GRK2 down-regulation in neutrophils, promotes survival in PLD2(-/-) mice. Furthermore, adoptively transferred PLD2(-/-) neutrophils significantly protect WT recipients against sepsis-induced death compared with transferred WT neutrophils. We suggest that PLD2 in neutrophils is essential for the pathogenesis of experimental sepsis and that pharmaceutical agents that target PLD2 may prove beneficial for septic patients.

© 2015 Lee et al.

 

PMID: 26282875 [PubMed - indexed for MEDLINE]
PMCID: PMC4548059 [Available on 2016-02-24]
(출처_PubMed)

 

 

배외식 교수(자연과학대학 생명과학과/ 삼성융합의과학원 겸직)는 면역세포의 이동성 제어에서 핵심 기능을 담당하는 chemoattractant 및 chemokine에 의한 면역반응 조절 및 이들을 이용한 감염 및 염증질환 치료제 개발에 대한 연구를 집중적으로 하고 있다. 특히, 선천면역 세포 활성 조절에 중요한 FPR (formyl peptide receptor)에 작용하는 리간드 개발을 통해 이들에 의한 패혈증, 류마티스 관절염, 대장염등의 염증성 질환 치료 효과와 이에 수반되는 작용기전에 대한 연구를 수행하고 있다. 본 연구실에서 집중적으로 연구하고 있는 FPR 리간드인 W펩타이드에 의한 패혈증 치료 효과는 제약회사에 기술이전을 완료하였으며, CXCR2등의 표적에 작용하는면역조절 물질에 의한 패혈증 치료 효과에 대한 연구를 활발히 진행하고 있다. 최근에는 PAMP (Pathogen-Associated Molecular Pattern) 및 DAMP (Danger-Associated Molecular Pattern)인식 수용체로서의 G-protein coupled receptor(GPCR)의 기능과 GPCR에 의한 Toll-like receptor의 활성 조절 기전 규명에 대해서도 심도 있는 연구를 수행하고 있다.   

  

▶ 배외식 교수 프로필

 

PubMed >  논문보기

 

BRIC > 한빛사논문 > 배외식    

 

 

※ 언론보도  

 

[보건복지부] 보도자료 "패혈증 치료를 위한 표적분자 규명 및 신약물질 발견" 

 

[YTN TV] 패혈증 신약 후보 물질, 국내서 첫 발견 - 2015.08.28

 

 

 

 

 

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