Neutrophils are the most abundant leukocytes in the circulation and the first responders to sites of infection. Using a neutrophil-deficient zebrafish, Professor Yiyue Zhang’s lab and Professor Wenqing Zhang’s lab made progress in the regulatory mechanism of neutrophil development and maturation. Their work demonstrates the important role of Alas1 in regulating neutrophil maturation and physiological function through the heme.

This work entitled “Alas1 is essential for neutrophil maturation in zebrafish” was published online in the journal Haematologica (doi:10.3324/haematol.2018.194316. June 15, 2018). Professor Yiyue Zhang and Professor Wenqing Zhang from Division of Cell, Developmental and Integrative Biology, School of Medicine are co-corresponding authors. The doctoral student Junwei Lian is the first author from Southern Medical University. This work was supported by the National Natural Science Foundation of China, and the Team Program of Guangdong Natural Science Foundation.

Neutrophils play essential roles in innate immunity. However, the complicated regulatory network of neutrophil development and maturation remains largely unknown. The team characterized a neutrophil-deficient mutant zebrafish line (previously named smu350) that was obtained by ENU mutagenesis and large-scale forward genetic screening, and found that alas1 was the causative gene of the smu350 mutant. Alas1 is the first and rate-limiting enzyme of the heme biosynthetic pathway. Heme functions as a prosthetic group on hemoproteins to activate their activities. Further study revealed that alas1 mutation caused heme deficiency in neutrophils, which led to neutrophil defects in zebrafish, including the loss of heme-related granule protein activities, defective granule formation, and altered immune responses against pathogenic bacteria. The results of this work enriched the knowledge on the regulatory mechanism of neutrophil development and maturation, and might also shed light on developing new drugs or treatment strategies for heme-related diseases.

Haematologica is the journal of the European Hematology Association, and publishes articles in the broad field of hematology, reporting on novel findings in basic, clinical and translational research. The 2017 impact factor of Haematologica is 9.090.

Full text link: https://doi.org/10.3324/haematol.2018.194316