Aged neutrophils contribute to the first line of defense in the acute inflammatory response.
Under steady-state conditions, aged neutrophils are removed from the circulation in bone marrow, liver, and spleen, thereby maintaining myeloid cell homeostasis. The fate of these aged immune cells under inflammatory conditions, however, remains largely obscure. Here, we demonstrate that in the acute inflammatory response during endotoxemia, aged neutrophils cease returning to the bone marrow and instead rapidly migrate to the site of inflammation. Having arrived in inflamed tissue, aged neutrophils were found to exhibit a higher phagocytic activity as compared with the subsequently recruited nonaged neutrophils. This distinct behavior of aged neutrophils under inflammatory conditions is dependent on specific age-related changes in their molecular repertoire that enable these "experienced" immune cells to instantly translate inflammatory signals into immune responses. In particular, aged neutrophils engage Toll-like receptor-4- and p38 MAPK-dependent pathways to induce conformational changes in β2 integrins that allow these phagocytes to effectively accomplish their mission in the front line of the inflammatory response. Hence, ageing in the circulation might represent a critical process for neutrophils that enables these immune cells to properly unfold their functional properties for host defense.
Walter Brendel Centre of Experimental Medicine.
Bernd
0000-0002-2615-0803
B
Uhl
Walter Brendel Centre of Experimental Medicine.
Yannick
Y
Vadlau
Walter Brendel Centre of Experimental Medicine.|Department of Otorhinolaryngology, Head and Neck Surgery, and.
Gabriele
G
Zuchtriegel
Walter Brendel Centre of Experimental Medicine.
Katharina
K
Nekolla
Walter Brendel Centre of Experimental Medicine.
Kariem
K
Sharaf
Department of Cardiology, Klinikum der Universität München, Ludwig-Maximilians-Universität München, Munich, Germany.
Florian
F
Gaertner
Department of Cardiology, Klinikum der Universität München, Ludwig-Maximilians-Universität München, Munich, Germany.
Steffen
S
Massberg
Walter Brendel Centre of Experimental Medicine.
Fritz
F
Krombach
Walter Brendel Centre of Experimental Medicine.|Department of Otorhinolaryngology, Head and Neck Surgery, and.
Christoph A
CA
Reichel
D000208:Acute Disease; D000818:Animals; D039481:CD11b Antigen / Q000378:metabolism; D002448:Cell Adhesion; D002462:Cell Membrane / Q000378:metabolism; D058948:Cell Tracking; D016922:Cellular Senescence; D016207:Cytokines / Q000378:metabolism; D007249:Inflammation / Q000276:immunology* / Q000473:pathology*; D016023:Integrins / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D009504:Neutrophils / Q000276:immunology*; D010587:Phagocytosis; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000378:metabolism
D039481:CD11b Antigen; D016207:Cytokines; D016023:Integrins; D017382:Reactive Oxygen Species; D051197:Toll-Like Receptor 4