Oxidant Signaling Mediated by Nox2 in Neutrophils Promotes Regenerative Myelopoiesis and Tissue Recovery following Ischemic Damage.
Oxidant Signaling Mediated by Nox2 in Neutrophils Promotes Regenerative Myelopoiesis and Tissue Recovery following Ischemic Damage.
复制标题
DOI：
10.4049/jimmunol.1800252
复制
发表时间：
2018-10-15
期刊：
影响因子：
--
通讯作者：
Urao N
中科院分区：
文献类型：
--
作者：
Fang MM;Barman PK;Thiruppathi M;Mirza RE;McKinney RD;Deng J;Christman JW;Du X;Fukai T;Ennis WJ;Koh TJ;Ushio-Fukai M;Urao N
缺血性组织损伤激活骨髓（BM）中的造血干细胞和祖细胞（HSPC），生成髓样细胞，持续的HSPC活性可能导致慢性炎症并损害组织恢复。尽管BM中增加的活性氧（ROS）调节HSPC功能，但它们在活化的HSPC的骨髓生成和随后的缺血性损伤期间的组织恢复中的作用尚不清楚。在此，我们报告了小鼠中Nox 2 NADPH氧化酶的缺失导致后肢缺血模型中BM HSPC活性和BM和缺血组织中炎性单核细胞/巨噬细胞水平持续升高。缺血性组织损伤诱导BM中的氧化剂，例如过氧化氢和氧化磷脂的升高，其以Nox 2依赖性方式激活氧化还原敏感性林恩激酶。此外，在缺血性损伤后的组织恢复期间，该Nox 2-R 0 S-Lyn激酶轴由归巢至BM的嗜中性粒细胞中的Nox 2诱导，其抑制HSPC活性和炎性单核细胞生成，并促进缺血性损伤后的组织再生。因此，由中性粒细胞中的Nox 2介导的BM中的氧化剂信号传导调节HSPC的骨髓生成以促进受损组织的再生。
Ischemic tissue damage activates hematopoietic stem and progenitor cells (HSPCs) in the bone marrow (BM) generating myeloid cells, and persistent HSPC activity may drive chronic inflammation and impair tissue recovery. Although increased reactive oxygen species (ROS) in the BM regulate HSPC functions, their roles in myelopoiesis of activated HSPCs and subsequent tissue recovery during ischemic damage are not well understood. Here, we report that deletion of Nox2 NADPH oxidase in mice results in persistent elevations in BM HSPC activity and levels of inflammatory monocytes/macrophages in BM and ischemic tissue in a model of hindlimb ischemia. Ischemic tissue damage induces oxidants in BM such as elevations of hydrogen peroxide and oxidized phospholipids, which activate redox-sensitive Lyn kinase in a Nox2-dependent manner. Moreover, during tissue recovery after ischemic injury, this Nox2-ROS-Lyn kinase axis is induced by Nox2 in neutrophils that home to the BM, which inhibits HSPC activity and inflammatory monocyte generation, and promotes tissue regeneration after ischemic damage. Thus, oxidant signaling in the BM mediated by Nox2 in neutrophils regulate myelopoiesis of HSPCs to promote regeneration of damaged tissue.
登录
查看更多内容
影响因子：
32.4
作者：
Campbell EL;Bruyninckx WJ;Kelly CJ;Glover LE;McNamee EN;Bowers BE;Bayless AJ;Scully M;Saeedi BJ;Golden-Mason L;Ehrentraut SF;Curtis VF;Burgess A;Garvey JF;Sorensen A;Nemenoff R;Jedlicka P;Taylor CT;Kominsky DJ;Colgan SP
通讯作者：
Colgan SP
膜联蛋白A1调节小鼠骨髓中巨噬细胞的中性粒细胞清除。
DOI：
10.1096/fj.11-182089
发表时间：
2012-01
期刊：
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
影响因子：
--
作者：
Dalli J;Jones CP;Cavalcanti DM;Farsky SH;Perretti M;Rankin SM
通讯作者：
Rankin SM
影响因子：
8.7
作者：
Huber, J;Vales, A;Leitinger, N
通讯作者：
Leitinger, N
影响因子：
5
作者：
Braunersreuther, Vincent;Montecucco, Fabrizio;Jaquet, Vincent
通讯作者：
Jaquet, Vincent
DOI：
10.1164/ajrccm.162.3.9906129
发表时间：
2000-09-01
影响因子：
24.7
作者：
Blackwell, TS;Yull, FE;Kerr, LD
通讯作者：
Kerr, LD