Expression and functional role of MDL-1 (CLEC5A) in mouse myeloid lineage cells
Expression and functional role of MDL-1 (CLEC5A) in mouse myeloid lineage cells
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DOI：
10.1189/jlb.0508329
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发表时间：
2009-03-01
影响因子：
5.5
通讯作者：
Tateno, Masatoshi
中科院分区：
文献类型：
--
作者：
Aoki, Naoko;Kimura, Yuka;Tateno, Masatoshi
髓系DNAX激活蛋白12 (DAP12)-关联凝集素-1 (MDL-1)，也称为c型凝集素结构域家族5，成员A，是c型凝集素家族的II型跨膜蛋白，与DAP12（也称为KARAP或TYROBP）结合。据报道，小鼠体内存在mdl -1的长型（MDL-1L）和短型（MDL-1S）两种亚型。此前，我们观察到小鼠肺分枝杆菌感染期间MDL-1 mRNA表达的显著诱导。这些数据表明，表达mdl -1的细胞参与了对分枝杆菌感染的免疫应答；然而，目前对MDL-1的功能知之甚少。在本研究中，我们证实了MDL-1L和MDL-1S蛋白在小鼠中性粒细胞和巨噬细胞中的显著表达。MDL-1L被n链聚糖和唾液酸高度糖基化。有趣的是，MDL-1的表达模式在中性粒细胞和巨噬细胞之间是不同的。在小鼠骨髓细胞系32Dcl3向中性粒细胞分化过程中，MDL-1的表达被显著诱导。此外，我们观察到MDL-1刺激在32Dcl3细胞中诱导了大量RANTES和巨噬细胞来源的趋化因子的产生，并通过TLR信号传导。MDL-1刺激也上调CD11b表达，维持细胞存活。因此，我们的研究结果表明，MDL-1在免疫防御中起着重要作用，这是先天免疫的结果，涉及中性粒细胞和巨噬细胞。j . Leukoc。生物学报。85:508-517；2009.
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. J. Leukoc. Biol. 85: 508-517; 2009.