Phenotypic and functional alterations of peripheral blood monocytes in neutrophil-specific granule deficiency

Journal of Leukocyte Biology

Takashi Yamazaki²  Adrian F. Gombart⁴  Atsushi Komiyama²  Yukio Sekiguchi²  Eiko Hidaka¹  Masaaki Shiohara²  Susumu Ito³  H. Phillip Koeffler⁴ 

[1] Laboratory Medicine and Laboratory Medicine and Laboratory Medicine and;Pediatrics and Pediatrics and Pediatrics and;Division of Blood Transfusion, Shinshu University School of Medicine, Matsumoto, Japan; and Division of Blood Transfusion, Shinshu University School of Medicine, Matsumoto, Japan; and Division of Blood Transfusion, Shinshu University School of Medicine, Matsumoto, Japan; and;Division of Hematology/Oncology, Cedars-Sinai Medical Center, Los Angeles, California Division of Hematology/Oncology, Cedars-Sinai Medical Center, Los Angeles, California Division of Hematology/Oncology, Cedars-Sinai Medical Center, Los Angeles, California

关键词: immunodeficiency;    C/EBPε;    CD14;    esterase;    IL-8;   

DOI  :  10.1189/jlb.0203063

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Neutrophil-specific granule deficiency (SGD) is a rare, congenital disease characterized by atypical neutrophil structure and function, resulting in recurrent bacterial infections from early infancy. Homozygous recessive mutations in the CCAAT/enhancer-binding protein ε (C/EBPε) gene were described in two of five SGD patients, indicating loss of C/EBPε function as the primary genetic defect in this disease. C/EBPε is expressed in murine and human macrophages. Macrophages from the C/EBPε-deficient mice show impaired differentiation, phagocytic activity, and transcription of macrophage-specific genes. To determine if monocyte/macrophage cells are impacted in SGD, we analyzed phenotypic features of peripheral blood (PB) monocytes in a SGD individual lacking functional C/EBPε. Flow cytometric analysis of PB leukocytes revealed aberrant expression of CD45, CD11b, CD14, CD15, and CD16 on cells from the SGD individual. Also, the PB CD14+ cells from this individual, weakly stained for the monocyte-specific enzyme, nonspecific esterase, and electron microscopic examination, indicated morphologic differences between the SGD cells and those from normal controls. Serum interleukin (IL)-6 levels in the SGD individual during a severe bacterial infection were lower compared with levels in other non-SGD individuals with sepsis. In contrast, serum IL-8 levels were markedly elevated in the SGD individual compared with those of non-SGD individuals in sepsis. PB CD14+ cells from the SGD individual expressed higher IL-8 mRNA levels compared with normal controls in response to lipopolysaccharide and interferon-γ. These phenotypic and functional alterations of PB monocytes in the SGD individual suggest that C/EBPε plays a critical role in monocyte/macrophage development of humans and is consistent with observations in the murine system. This study implicates abnormalities in monocytes/macrophages and neutrophils in the onset and development of SGD.

【 授权许可】

Unknown