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必发彩票中国医学科学院北京协和医学院血液病医院(血液学研究所)(以下简称“院所”)由中国血液学创始人邓家栋教授创建于1957年。七十年代迁往四川,1982年重新迁回天津。   90年代以来,随着我国血液学事业的发展和医疗市场的变化,院所不断开拓创新,必发彩票谋求血液学事业的新发展。从容不从众,追求创新,精髓不变是我们的办院方针。为把医院做“特”,科研做“精”,我们改“大所小院”为“大院小所”,由过去200张床位的“小综合”,发展为600余张床位的血液病“大专科”,由过去一个大血液内科发展为按病种和功能设置的12个临床中心的专科医院;以实验血液学国家重点实验室为龙头,围绕实验血液学和干细胞研究凝炼研究方向,建立了精干的基础研究队伍。

 
重点实验室许元富和罗鸿博课题组合作研究成果发表在JCI期刊上

  我重点实验室许元富研究员和兼职研究员罗鸿博教授的合作研究成果在近期的J CLIN INVEST期刊上发表,论文题目为“Proteinase 3-dependent caspase-3 cleavage modulates neutrophil death and inflammation”。

Abstract

  Caspase-3-mediated spontaneous death in neutrophils is a prototype of programmed cell death and is critical for modulating physiopathological inflammatory responses; however, the underlying regulatory pathways remain ill defined. Here we determined that in aging neutrophils, the cleavage and activation of caspase-3 is independent of the canonical caspase-8- or caspase-9-mediated pathway. Instead, caspase-3 activation was mediated by serine protease proteinase 3 (PR3), which is present in the cytosol of aging neutrophils. Specifically, PR3 cleaved procaspase-3 at a site upstream of the canonical caspase-9 cleavage site. In mature neutrophils, PR3 was sequestered in granules and released during aging via lysosomal membrane permeabilization (LMP), leading to procaspase-3 cleavage and apoptosis. Pharmacological inhibition or knockdown of PR3 delayed neutrophil death in vitro and consistently delayed neutrophil death and augmented neutrophil accumulation at sites of inflammation in a murine model of peritonitis. Adoptive transfer of both WT and PR3-deficient neutrophils revealed that the delayed death of neutrophils lacking PR3 is due to an altered intrinsic apoptosis/survival pathway, rather than the inflammatory microenvironment. The presence of the suicide protease inhibitor SERPINB1 counterbalanced the protease activity of PR3 in aging neutrophils, and deletion of Serpinb1 accelerated neutrophil death. Taken together, our results reveal that PR3-mediated caspase-3 activation controls neutrophil spontaneous death.

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