Age-related changes in the local milieu of inflamed tissues cause aberrant neutrophil trafficking and subsequent remote organ damage

被引：110

作者：

Barkaway, Anna ^{[1
]}

Rolas, Loic ^{[1
]}

Joulia, Regis ^{[1
]}

Bodkin, Jennifer ^{[1
]}

Lenn, Tchern ^{[1
]}

Owen-Woods, Charlotte ^{[1
]}

Reglero-Real, Natalia ^{[1
]}

Stein, Monja ^{[1
]}

Vazquez-Martinez, Laura ^{[1
]}

Girbl, Tamara ^{[1
]}

Poston, Robin N. ^{[1
]}

Golding, Matthew ^{[1
]}

Saleeb, Rebecca S. ^{[1
]}

Thiriot, Aude ^{[2
,3
,4
]}

von Andrian, Ulrich H. ^{[2
,3
,4
]}

Duchene, Johan ^{[5
]}

Voisin, Mathieu-Benoit ^{[1
]}

Bishop, Cleo L. ^{[6
]}

Voehringer, David ^{[7
,8
]}

Roers, Axel ^{[9
]}

Rot, Antal ^{[1
,10
]}

Laemmermann, Tim ^{[11
]}

Nourshargh, Sussan ^{[1
,10
]}

机构：

[1] Queen Mary Univ London, Ctr Microvasc Res, Barts & London Sch Med & Dent, William Harvey Res Inst, London EC1M 6BQ, England

[2] Harvard Med Sch, Dept Immunol, Boston, MA 02115 USA

[3] Harvard Med Sch, HMS Ctr Immune Imaging, Boston, MA 02115 USA

[4] Ragon Inst MGH MIT & Harvard, Cambridge, MA 02139 USA

[5] Ludwig Maximillians Univ LMU Munchen, Inst Cardiovasc Prevent IPEK, D-80336 Munich, Germany

[6] Queen Mary Univ London, Ctr Cell Biol & Cutaneous Res, Barts & London Sch Med & Dent, Blizard Inst, London E1 2AT, England

[7] Univ Hosp Erlangen, Dept Infect Biol, D-91054 Erlangen, Germany

[8] Friedrich Alexander Univ Erlangen Nuremberg FAU, D-91054 Erlangen, Germany

[9] Tech Univ Dresden, Med Fac Carl Gustav Carus, Inst Immunol, D-01069 Dresden, Germany

[10] Queen Mary Univ London, Ctr Inflammat & Therapeut Innovat, Barts & London Sch Med & Dent, London EC1M 6BQ, England

[11] Max Planck Inst Immunobiol & Epigenet, Freiburg, Germany

来源：

IMMUNITY | 2021年 / 54卷 / 07期

基金：

欧盟第七框架计划; 英国惠康基金;

关键词：

MAST-CELLS; LEUKOCYTE MIGRATION; INFLAMMATION; ADHESION; RECEPTOR; CHEMOKINES; PROTEIN; CXCR2; DYSREGULATION; RECRUITMENT;

D O I：

10.1016/j.immuni.2021.04.025

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Aging is associated with dysregulated immune functions. Here, we investigated the impact of age on neutrophil diapedesis. Using confocal intravital microscopy, we found that in aged mice, neutrophils adhered to vascular endothelium in inflamed tissues but exhibited a high frequency of reverse transendothelial migration (rTEM). This retrograde breaching of the endothelium by neutrophils was governed by enhanced production of the chemokine CXCL1 from mast cells that localized at endothelial cell (EC) junctions. Increased EC expression of the atypical chemokine receptor 1 (ACKR1) supported this pro-inflammatory milieu in aged venules. Accumulation of CXCL1 caused desensitization of the chemokine receptor CXCR2 on neutrophils and loss of neutrophil directional motility within EC junctions. Fluorescent tracking revealed that in aged mice, neutrophils undergoing rTEM re-entered the circulation and disseminated to the lungs where they caused vascular leakage. Thus, neutrophils stemming from a local inflammatory site contribute to remote organ damage, with implication to the dysregulated systemic inflammation associated with aging.

引用

页码：1494 / +

页数：24

共 60 条

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