PMID- 35532955
OWN - NLM
STAT- MEDLINE
DCOM- 20220909
LR  - 20221003
IS  - 1557-8518 (Electronic)
IS  - 1540-4196 (Linking)
VI  - 20
IP  - 7
DP  - 2022 Sep
TI  - Nonalcoholic Fatty Liver Disease Patients Exhibit Reduced CD47 and Increased 
      Sphingosine, Cholesterol, and Monocyte Chemoattractant Protein-1 Levels in the 
      Erythrocyte Membranes.
PG  - 377-383
LID - 10.1089/met.2022.0006 [doi]
AB  - Background: Nonalcoholic fatty liver disease (NAFLD) constitutes a significant 
      cause of deaths, liver transplantations, and economic costs worldwide. Despite 
      extended research, investigations on the role of erythrocytes are scarce. Red 
      blood cells from experimental animals and human patients with NAFLD present 
      phosphatidylserine exposure, which is then recognized by Kupffer cells. This 
      event leads to erythrophagocytosis and amplification of inflammation through iron 
      disposition. In addition, it has been shown that erythrocytes from NAFLD patients 
      release the chemokine monocyte chemoattractant protein-1 (MCP1), leading to 
      increased tumor necrosis factor alpha release from macrophages RAW 264.7. 
      However, erythrophagocytosis can also be caused by reduced CD47 levels. Moreover, 
      increased MCP1 release could be either signal-induced or caused by higher MCP1 
      levels on the erythrocyte membrane. Finally, erythrocyte efferocytosis could 
      provide additional inflammatory metabolites. Methods: In this study, we measured 
      the erythrocyte membrane levels of CD47 and MCP1 by enzyme-linked immunosorbent 
      assay, and cholesterol and sphingosine with thin-layer chromatography. Eighteen 
      patients (8 men and 10 women, aged 56.7 +/- 11.5 years) and 14 healthy controls (7 
      men and 7 women, aged 39.3 +/- 15.6 years) participated in our study. Results: The 
      erythrocyte CD47 levels were decreased in the erythrocyte membranes of NAFLD 
      patients (844 +/- 409 pg/mL) compared with healthy controls (2969 +/- 1936 pg/mL) 
      with P = 0.012. Levels of MCP1 increased in NAFLD patients (389 +/- 255 pg/mL) 
      compared with healthy controls (230 +/- 117 pg/mL) with P = 0.0274, but low 
      statistical power. Moreover, in erythrocyte membranes, there was a statistically 
      significant accumulation of sphingosine and cholesterol in NAFLD patients 
      compared with healthy controls. Conclusions: Our results imply that erythrocytes 
      release chemotactic "find me" signals (MCP1) while containing reduced "do not eat 
      me" signals (CD47). These molecules can lead to erythrophagocytosis. Next, 
      increased "goodbye" signals (sphingosine and cholesterol) could augment 
      inflammation by metabolic reprogramming.
FAU - Papadopoulos, Charalampos
AU  - Papadopoulos C
AD  - Laboratory of Biochemistry, Department of Basic Sciences, School of Medicine, 
      Democritus University of Thrace, Alexandroupolis, Greece.
FAU - Spourita, Eleftheria
AU  - Spourita E
AD  - Laboratory of Biochemistry, Department of Basic Sciences, School of Medicine, 
      Democritus University of Thrace, Alexandroupolis, Greece.
FAU - Mimidis, Konstantinos
AU  - Mimidis K
AD  - First Department of Internal Medicine, School of Medicine, Democritus University 
      of Thrace, Alexandroupolis, Greece.
FAU - Kolios, George
AU  - Kolios G
AUID- ORCID: 0000-0002-2066-4782
AD  - Laboratory of Pharmacology, Department of Basic Sciences, School of Medicine, 
      Democritus University of Thrace, Alexandroupolis, Greece.
FAU - Tentes, Loannis
AU  - Tentes L
AD  - Laboratory of Biochemistry, Department of Basic Sciences, School of Medicine, 
      Democritus University of Thrace, Alexandroupolis, Greece.
FAU - Anagnostopoulos, Konstantinos
AU  - Anagnostopoulos K
AUID- ORCID: 0000-0002-3985-9176
AD  - Laboratory of Biochemistry, Department of Basic Sciences, School of Medicine, 
      Democritus University of Thrace, Alexandroupolis, Greece.
LA  - eng
PT  - Journal Article
DEP - 20220509
PL  - United States
TA  - Metab Syndr Relat Disord
JT  - Metabolic syndrome and related disorders
JID - 101150318
RN  - 0 (CD47 Antigen)
RN  - 0 (CD47 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - NGZ37HRE42 (Sphingosine)
SB  - IM
MH  - Adult
MH  - Aged
MH  - CD47 Antigen/metabolism
MH  - Chemokine CCL2/metabolism
MH  - Cholesterol/chemistry
MH  - Erythrocyte Membrane/chemistry
MH  - Female
MH  - Humans
MH  - Inflammation/metabolism
MH  - Liver/metabolism
MH  - Male
MH  - Middle Aged
MH  - *Non-alcoholic Fatty Liver Disease/pathology
MH  - Sphingosine/chemistry
OTO - NOTNLM
OT  - NAFLD
OT  - immunometabolism
OT  - inflammation
OT  - metabolic syndrome
OT  - red blood cell
EDAT- 2022/05/10 06:00
MHDA- 2022/09/11 06:00
CRDT- 2022/05/09 11:43
PHST- 2022/05/10 06:00 [pubmed]
PHST- 2022/09/11 06:00 [medline]
PHST- 2022/05/09 11:43 [entrez]
AID - 10.1089/met.2022.0006 [doi]
PST - ppublish
SO  - Metab Syndr Relat Disord. 2022 Sep;20(7):377-383. doi: 10.1089/met.2022.0006. 
      Epub 2022 May 9.