Retention of functional mitochondria in mature red blood cells from patients with sickle cell disease.
Journal
British journal of haematology
ISSN: 1365-2141
Titre abrégé: Br J Haematol
Pays: England
ID NLM: 0372544
Informations de publication
Date de publication:
08 2022
08 2022
Historique:
revised:
26
04
2022
received:
02
03
2022
accepted:
17
05
2022
pubmed:
8
6
2022
medline:
28
7
2022
entrez:
7
6
2022
Statut:
ppublish
Résumé
Sickle cell disease (SCD) is an inherited blood disorder characterized by sickled red blood cells (RBCs), which are more sensitive to haemolysis and can contribute to disease pathophysiology. Although treatment of SCD can include RBC transfusion, patients with SCD have high rates of alloimmunization. We hypothesized that RBCs from patients with SCD have functionally active mitochondria and can elicit a type 1 interferon response. We evaluated blood samples from more than 100 patients with SCD and found elevated frequencies of mitochondria in reticulocytes and mature RBCs, as compared to healthy blood donors. The presence of mitochondria in mature RBCs was confirmed by flow cytometry, electron microscopy, and proteomic analysis. The mitochondria in mature RBCs were metabolically competent, as determined by enzymatic activities and elevated levels of mitochondria-derived metabolites. Metabolically-active mitochondria in RBCs may increase oxidative stress, which could facilitate and/or exacerbate SCD complications. Coculture of mitochondria-positive RBCs with neutrophils induced production of type 1 interferons, which are known to increase RBC alloimmunization rates. These data demonstrate that mitochondria retained in mature RBCs are functional and can elicit immune responses, suggesting that inappropriate retention of mitochondria in RBCs may play an underappreciated role in SCD complications and be an RBC alloimmunization risk factor.
Identifiants
pubmed: 35670632
doi: 10.1111/bjh.18287
pmc: PMC9329257
mid: NIHMS1814737
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
574-586Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL146442
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL133325
Pays : United States
Organisme : NHLBI NIH HHS
ID : K08 HL141446
Pays : United States
Organisme : NIH HHS
ID : S10 OD020056
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL148151
Pays : United States
Organisme : NHLBI NIH HHS
ID : R21 HL150032
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL149714
Pays : United States
Informations de copyright
© 2022 British Society for Haematology and John Wiley & Sons Ltd.
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