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Originally published online as doi:10.1189/jlb.0508329 on December 12, 2008

Published online before print December 12, 2008
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(Journal of Leukocyte Biology. 2009;85:508-517.)
© 2009 by Society for Leukocyte Biology

Expression and functional role of MDL-1 (CLEC5A) in mouse myeloid lineage cells

Naoko Aoki*,1, Yuka Kimura*, Shoji Kimura{dagger}, Toshihiro Nagato*, Makoto Azumi*, Hiroya Kobayashi*, Keisuke Sato* and Masatoshi Tateno*

* Department of Pathology and
{dagger} School of Nursing, Asahikawa Medical College, Asahikawa, Japan

1 Correspondence: Department of Pathology, Asahikawa Medical College, Midorigaoka-higashi 2-1-1-1, Asahikawa, Japan. E-mail: aoq{at}asahikawa-med.ac.jp

Myeloid DNAX activation protein 12 (DAP12)-associating lectin-1 (MDL-1), also known as C-type lectin domain family 5, member A, is a type II transmembrane protein belonging to the C-type lectin family and associates with DAP12 (also called KARAP or TYROBP). It has been reported that two isoforms of MDL-1—long form (MDL-1L) and short form (MDL-1S)—exist in mice. Previously, we observed the marked induction of MDL-1 mRNA expression during the pulmonary mycobacterial infection in mice. The data suggested that the MDL-1-expressing cells were involved in immune responses against mycobacterial infection; however, little is known about the function of MDL-1 as yet. In this study, we demonstrated the significant protein expression of MDL-1L and MDL-1S in mouse neutrophils and macrophages. MDL-1L was highly glycosylated by N-linked glycan and sialic acid. Interestingly, the expression pattern of MDL-1 was different between neutrophils and macrophages. MDL-1 expression was notably induced during the differentiation of the mouse myeloid cell line 32Dcl3 into neutrophils. Additionally, we observed that MDL-1 stimulation induced a significant amount of RANTES and macrophage-derived chemokine production in 32Dcl3 cells in cooperation with signaling through TLR. MDL-1 stimulation also up-regulated CD11b expression and maintained cell survival. Our findings indicate that MDL-1, therefore, plays an important role in immune defense as a result of an innate immunity, which involves neutrophils and macrophages.

Key Words: DAP12 • DAP10 • innate immunity • Toll-like receptor