Impaired mast cell maturation and degranulation and attenuated allergic responses in Ndrg1-deficient mice.

Abstract

We have previously reported that N-myc downstream regulated gene-1 (NDRG1) is an early inducible protein during the maturation of mouse bone marrow-derived mast cells (BMMCs) toward a connective tissue mast cell-like phenotype. To clarify the function of NDRG1 in mast cells and allergic responses, we herein analyzed mast cell-associated phenotypes of mice lacking the Ndrg1 gene. Allergic responses including IgE-mediated passive systemic and cutaneous anaphylactic reactions were markedly attenuated in Ndrg1-deficient mice as compared with those in wild-type mice. In Ndrg1-deficient mice, dermal and peritoneal mast cells were decreased in number and morphologically abnormal with impaired degranulating ability. Ex vivo, Ndrg1-deficient BMMCs cocultured with Swiss 3T3 fibroblasts in the presence of stem cell factor, a condition that facilitates the maturation of BMMCs toward a CTMC-like phenotype, displayed less exocytosis than replicate wild-type cells after the cross-linking of FcepsilonRI or stimulation with compound 48/80, even though the exocytotic response of IL-3-maintained, immature BMMCs from both genotypes was comparable. Unlike degranulation, the production of leukotriene and cytokines by cocultured BMMCs was unaffected by NDRG1 deficiency. Taken together, the altered phenotypes of Ndrg1-deficient mast cells both in vivo and ex vivo suggest that NDRG1 has roles in the terminal maturation and effector function (degranulation) of mast cells.

• Authors: Yoshitaka Taketomi, Kohei Sunaga, Satoshi Tanaka, Masanori Nakamura, Satoru Arata, Tomohiko Okuda, Tae-Chul Moon, Hyeun-Wook Chang, Yukihiko Sugimoto, Koichi Kokame, Toshiyuki Miyata, Makoto Murakami, Ichiro Kudo
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 178 Issue 11 Pg. 7042-53 (Jun 01 2007) ISSN: 0022-1767 [Print] United States
• PMID: 17513753 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cell Cycle Proteins
• Intracellular Signaling Peptides and Proteins
• N-myc downstream-regulated gene 1 protein

Topics

• Anaphylaxis (genetics, immunology, pathology)
• Animals
• Bone Marrow Cells (immunology, metabolism, pathology)
• Cell Cycle Proteins (genetics, physiology)
• Cell Degranulation (genetics, immunology)
• Cell Differentiation (genetics, immunology)
• Cells, Cultured
• Coculture Techniques
• Cytoplasmic Granules (genetics, immunology, pathology)
• Exocytosis (genetics, immunology)
• Fibroblasts (immunology, metabolism)
• Immunophenotyping
• Intracellular Signaling Peptides and Proteins (deficiency, genetics, physiology)
• Mast Cells (immunology, metabolism, pathology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Mice, Mutant Strains
• Passive Cutaneous Anaphylaxis (genetics, immunology)