PUBLICATION
Alas1 is essential for neutrophil maturation in zebrafish
- Authors
- Lian, J., Chen, J., Wang, K., Zhao, L., Meng, P., Yang, L., Wei, J., Ma, N., Xu, J., Zhang, W., Zhang, Y.
- ID
- ZDB-PUB-180630-3
- Date
- 2018
- Source
- Haematologica 103(11): 1785-1795 (Journal)
- Registered Authors
- Lian, Junwei, Ma, Ning, Meng, Ping, Wang, Kun, Zhang, Wenqing, Zhang, Yiyue, Zhao, Lingfeng
- Keywords
- Granulocytes, Monocytes, Macrophages, Hematopoiesis, Heme, alas1
- MeSH Terms
-
- 5-Aminolevulinate Synthetase*/genetics
- 5-Aminolevulinate Synthetase*/immunology
- Animals
- Escherichia coli/genetics
- Escherichia coli/immunology
- Escherichia coli Infections/genetics
- Escherichia coli Infections/immunology
- Escherichia coli Infections/pathology
- Fish Diseases/genetics
- Fish Diseases/immunology
- Fish Diseases/microbiology
- Fish Diseases/pathology
- Heme/genetics
- Heme/immunology
- Neutrophils/immunology*
- Neutrophils/pathology
- Zebrafish*/immunology
- Zebrafish*/microbiology
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/immunology
- PubMed
- 29954941 Full text @ Haematologica
Citation
Lian, J., Chen, J., Wang, K., Zhao, L., Meng, P., Yang, L., Wei, J., Ma, N., Xu, J., Zhang, W., Zhang, Y. (2018) Alas1 is essential for neutrophil maturation in zebrafish. Haematologica. 103(11):1785-1795.
Abstract
Neutrophils play essential roles in innate immunity and are the first responders to kill foreign micro-organisms, a function that partially depends on their granule content. The complicated regulatory network of neutrophil development and maturation remains largely unknown. Here we utilized neutrophil-deficient zebrafish to identify a novel role of Alas1, a heme biosynthesis pathway enzyme, in neutrophil development. We showed that Alas1-deficient zebrafish exhibited proper neutrophil initiation, but further neutrophil maturation was blocked due to heme deficiency, with lipid storage and granule formation deficiencies, and loss of heme-dependent granule protein activities. Consequently, Alas1-deficient zebrafish showed impaired bactericidal ability and augmented inflammatory responses when challenged with Escherichia coli These findings demonstrate the important role of Alas1 in regulating neutrophil maturation and physiological function through the heme. Our study provides an in vivo model of Alas1 deficiency and may be useful to evaluate the progression of heme-related disorders in order to facilitate the development of drugs and treatment strategies for these diseases.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping