PMID- 35411633
OWN - NLM
STAT- MEDLINE
DCOM- 20221003
LR  - 20221106
IS  - 1938-3673 (Electronic)
IS  - 0741-5400 (Linking)
VI  - 112
IP  - 4
DP  - 2022 Oct
TI  - Erythrocyte-derived extracellular vesicles aggravate inflammation by promoting 
      the proinflammatory macrophage phenotype through TLR4-MyD88-NF-kappaB-MAPK pathway.
PG  - 693-706
LID - 10.1002/JLB.3A0821-451RR [doi]
AB  - Transfusion of stored erythrocytes is associated with the increased risk of 
      morbidity and mortality in critical infections, but the mechanism is incompletely 
      understood. Previous studies have suggested that RBC-derived extracellular 
      vesicles (EVs) may be potential risk factors for the occurrence of 
      transfusion-related immunomodulation. The purpose of our study was to evaluate 
      the effects of RBC-derived EVs under inflammatory conditions and explore the 
      underlying mechanisms. In vivo, the activity of EVs was evaluated in cecal 
      ligation and puncture (CLP)-induced sepsis. Our results showed that EVs 
      significantly aggravated the inflammatory response to sepsis in serum and lung 
      tissue by promoting the production of the proinflammatory factors tumor necrosis 
      factor-alpha (TNF-alpha）-interleukin-6(IL-6), and interleukin-1beta (IL-1beta) and reduced the 
      survival rate of septic mice in vivo. Importantly, adoptive transfer of 
      EVs-pretreated bone marrow-derived macrophages (BMDMs) obviously aggravated 
      systemic proinflammatory factors in mice after CLP surgery. In vitro, the 
      proinflammatory properties of EVs were shown to elevate TNF-alpha, IL-6, and IL-1beta 
      levels in lipopolysaccharide (LPS)-stimulated BMDMs. Moreover, EVs promoted 
      LPS-induced macrophage polarization into a proinflammatory phenotype. The 
      underlying mechanism might involve EV-mediated up-regulation of 
      TLR4-MyD88-NF-kappaB-MAPK activity to favor macrophage cytokine production.
CI  - (c)2022 Society for Leukocyte Biology.
FAU - Gao, Yuhan
AU  - Gao Y
AD  - Department of Blood Transfusion, Peking University People's Hospital, Beijing, 
      China.
FAU - Jin, Haiqiang
AU  - Jin H
AD  - Department of Neurology, Peking University First Hospital, Beijing, China.
FAU - Tan, Hui
AU  - Tan H
AD  - Department of Neurosurgery, Shenzhen Second People's Hospital, Shenzhen, China.
FAU - Cai, Xiaodong
AU  - Cai X
AD  - Department of Neurosurgery, Shenzhen Second People's Hospital, Shenzhen, China.
FAU - Sun, Yongan
AU  - Sun Y
AD  - Department of Neurology, Peking University First Hospital, Beijing, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220412
PL  - England
TA  - J Leukoc Biol
JT  - Journal of leukocyte biology
JID - 8405628
RN  - 0 (Interleukin-1beta)
RN  - 0 (Interleukin-6)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Myd88 protein, mouse)
RN  - 0 (Myeloid Differentiation Factor 88)
RN  - 0 (NF-kappa B)
RN  - 0 (Tlr4 protein, mouse)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Animals
MH  - Erythrocytes
MH  - *Extracellular Vesicles/metabolism
MH  - Inflammation
MH  - Interleukin-1beta/metabolism
MH  - Interleukin-6/metabolism
MH  - Lipopolysaccharides/pharmacology
MH  - Macrophages/metabolism
MH  - Mice
MH  - Myeloid Differentiation Factor 88/metabolism
MH  - NF-kappa B/metabolism
MH  - Phenotype
MH  - *Sepsis
MH  - Toll-Like Receptor 4/metabolism
MH  - Tumor Necrosis Factor-alpha/metabolism
OTO - NOTNLM
OT  - extracellular vesicle
OT  - inflammatory response
OT  - macrophage
EDAT- 2022/04/13 06:00
MHDA- 2022/10/04 06:00
CRDT- 2022/04/12 05:33
PHST- 2022/03/12 00:00 [revised]
PHST- 2021/08/23 00:00 [received]
PHST- 2022/04/13 06:00 [pubmed]
PHST- 2022/10/04 06:00 [medline]
PHST- 2022/04/12 05:33 [entrez]
AID - 10.1002/JLB.3A0821-451RR [doi]
PST - ppublish
SO  - J Leukoc Biol. 2022 Oct;112(4):693-706. doi: 10.1002/JLB.3A0821-451RR. Epub 2022 
      Apr 12.