Functional characteristics of circulating granulocytes in severe congenital neutropenia caused by ELANE mutations.
Bone Marrow Cells
/ physiology
Child, Preschool
Codon, Terminator
Congenital Bone Marrow Failure Syndromes
/ blood
Eosinophils
/ enzymology
Female
Frameshift Mutation
Glucose-6-Phosphatase
/ genetics
Granulocytes
/ enzymology
Humans
Infant
Leukocyte Count
Leukocyte Elastase
/ genetics
Male
NADPH Oxidases
/ metabolism
Neutropenia
/ blood
Neutrophils
/ metabolism
Point Mutation
Reactive Oxygen Species
/ metabolism
Eosinophils
Granulocytes
Neutrophils
Reactive oxygen species
SCN1
Journal
BMC pediatrics
ISSN: 1471-2431
Titre abrégé: BMC Pediatr
Pays: England
ID NLM: 100967804
Informations de publication
Date de publication:
08 06 2019
08 06 2019
Historique:
received:
17
12
2018
accepted:
22
05
2019
entrez:
10
6
2019
pubmed:
10
6
2019
medline:
4
7
2020
Statut:
epublish
Résumé
Neutrophils and eosinophils are multifunctional granulocytes derived from common myelocytic-committed progenitor cells. Severe congenital neutropenia 1 (SCN1) caused by ELANE mutations is a rare disease characterized by very low numbers of circulating neutrophils. Little is known about the functional characteristics of the SCN1 granulocytes, except that eosinophilia has been noticed in both bone marrow and peripheral blood. In this study, we profiled the number and function of granulocytes in patients suffering from SCN1. Nine patients diagnosed with SCN1 were enrolled in this study and absolute counts of eosinophils and neutrophils from bone marrow aspirates and peripheral blood samples were analysed. In addition, Ficoll-Paque enriched granulocytes from patients and healthy controls were analysed for specific eosinophil and neutrophil markers using flow cytometry and for NADPH-oxidase activity-profile by chemiluminescence. Our data demonstrate a skewed granulocyte population in SCN1 patients dominated by eosinophils in both bone marrow and peripheral blood. The latter was detected only by blood smear examination, but not by automated blood analysers. Furthermore, we show that the SCN1 eosinophils exerted normal production of reactive oxygen species generated by the NADPH-oxidase, however the response was profoundly different from that of healthy control neutrophils. SCN1 patients with ELANE mutations suffer from neutropenia yet display eosinophilia in the bone marrow and blood, as revealed by smear examination but not by automatic blood analysers. The SCN1 eosinophils are functionally normal regarding production of reactive oxygen species (ROS). However, the ROS profile produced by eosinophils differs drastically from that of neutrophils isolated from the same blood donor, implying that the eosinophilia in SCN1 cannot compensate for the loss of neutrophils regarding ROS-mediated functions.
Sections du résumé
BACKGROUND
Neutrophils and eosinophils are multifunctional granulocytes derived from common myelocytic-committed progenitor cells. Severe congenital neutropenia 1 (SCN1) caused by ELANE mutations is a rare disease characterized by very low numbers of circulating neutrophils. Little is known about the functional characteristics of the SCN1 granulocytes, except that eosinophilia has been noticed in both bone marrow and peripheral blood. In this study, we profiled the number and function of granulocytes in patients suffering from SCN1.
METHODS
Nine patients diagnosed with SCN1 were enrolled in this study and absolute counts of eosinophils and neutrophils from bone marrow aspirates and peripheral blood samples were analysed. In addition, Ficoll-Paque enriched granulocytes from patients and healthy controls were analysed for specific eosinophil and neutrophil markers using flow cytometry and for NADPH-oxidase activity-profile by chemiluminescence.
RESULTS
Our data demonstrate a skewed granulocyte population in SCN1 patients dominated by eosinophils in both bone marrow and peripheral blood. The latter was detected only by blood smear examination, but not by automated blood analysers. Furthermore, we show that the SCN1 eosinophils exerted normal production of reactive oxygen species generated by the NADPH-oxidase, however the response was profoundly different from that of healthy control neutrophils.
CONCLUSIONS
SCN1 patients with ELANE mutations suffer from neutropenia yet display eosinophilia in the bone marrow and blood, as revealed by smear examination but not by automatic blood analysers. The SCN1 eosinophils are functionally normal regarding production of reactive oxygen species (ROS). However, the ROS profile produced by eosinophils differs drastically from that of neutrophils isolated from the same blood donor, implying that the eosinophilia in SCN1 cannot compensate for the loss of neutrophils regarding ROS-mediated functions.
Identifiants
pubmed: 31176364
doi: 10.1186/s12887-019-1556-x
pii: 10.1186/s12887-019-1556-x
pmc: PMC6555947
doi:
Substances chimiques
Codon, Terminator
0
Reactive Oxygen Species
0
NADPH Oxidases
EC 1.6.3.-
Glucose-6-Phosphatase
EC 3.1.3.9
G6PC3 protein, human
EC 3.1.3.9.
ELANE protein, human
EC 3.4.21.37
Leukocyte Elastase
EC 3.4.21.37
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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