Frontline Science: Mast cells regulate neutrophil homeostasis by influencing macrophage clearance activity

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

article

Elena Jachetti¹  Federica D'Incಠ Luca Danelli²  Raffaella Magris²  Chiara Dal Secco²  Filippo Vit²  Valeria Cancila³  Claudio Tripodo³  Patrizia Scapini⁴  Mario Paolo Colombo¹  Carlo Pucillo²  Barbara Frossi² 

[1] Molecular Immunology Unit, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori;Immunology Section, Department of Medicine, University of Udine;Tumor Immunology Unit, Department of Health Sciences, University of Palermo;Division of General Pathology, University of Verona

关键词: Kit (W-sh) mice;    macrophages;    mast cell;    neutrophils;    phagocytosis;   

DOI  :  10.1002/JLB.4HI1018-390R

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

The receptor tyrosine kinase cKit and its ligand stem cell factor are essential for mast cells (MC) development and survival. Strains with mutations affecting the Kit gene display a profound MC deficiency in all tissues and have been extensively used to investigate the role of MC in both physiologic and pathologic conditions. However, these mice present a variety of abnormalities in other immune cell populations that can affect the interpretation of MC-related responses. C57BL/6 KitW-sh are characterized by an aberrant extramedullary myelopoiesis and systemic neutrophilia. MC deficiency in KitW-sh mice can be selectively repaired by engraftment with in vitro-differentiated MC to validate MC-specific functions. Nevertheless, the impact of MC reconstitution on other immune populations has never been evaluated in detail. Here, we specifically investigated the neutrophil compartment in primary and secondary lymphoid organs of C57BL/6 KitW-sh mice before and after MC reconstitution. We found that, albeit not apparently affecting neutrophils phenotype or maturation, MC reconstitution of KitW-sh mice restored the number of neutrophils at a level similar to that of wild-type C57BL/6 mice. In vitro and ex vivo experiments indicated that MC can influence neutrophil clearance by increasing macrophages’ phagocytic activity. Furthermore, the G-CSF/IL-17 axis was also influenced by the presence or absence of MC in KitW-sh mice. These data suggest that MC play a role in the control of neutrophil homeostasis and that this aspect should be taken into account in the interpretation of results obtained using KitW-sh mice.

【 授权许可】

CC BY