Deletion polymorphism of SIGLEC14 and its functional implications.
Human Siglec-14, a member of the Siglec family of sialic acid-binding lectins, shows extensive sequence similarity to human Siglec-5. To analyze respective expression patterns of Siglec-14 and Siglec-5, we developed specific antibodies against each of them. We found that the former was expressed on granulocytes and monocytes, while the latter was on granulocytes and B-cells. Surprisingly, some individuals lacked the expression of Siglec-14, while they all expressed Siglec-5. We found that a fusion between SIGLEC14 and SIGLEC5 genes, resulting in the functional deletion of SIGLEC14, underlies this phenotype. The presence of the "SIGLEC14 null" allele in all human populations we tested implies an ancient origin, while its allelic frequency is higher in Asians compared with Africans and Europeans. The forced expression of Siglec-14 in a monocytic cell line-enhanced TNF-alpha secretion elicited by lipopolysaccharide. These results imply that Siglec-14 may play some role in bacterial infection.
Research Center for Medical Glycoscience, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki, Japan.
Masahiro
M
Yamanaka
Yukinari
Y
Kato
Takashi
T
Angata
Hisashi
H
Narimatsu
D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics / Q000378:metabolism*; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D050939:Gene Fusion; D006098:Granulocytes / Q000276:immunology / Q000378:metabolism; D006801:Humans; D037102:Lectins / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D011110:Polymorphism, Genetic; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D037102:Lectins; D008070:Lipopolysaccharides; D011956:Receptors, Cell Surface; C514213:SIGLEC14 protein, human; C114531:SIGLEC5 protein, human; D014409:Tumor Necrosis Factor-alpha