Chiou Shean-Jaw, Wang Chan-Chi, Tseng Yan-Shen, Lee Yen-Jung, Chen Shih-Chieh, Chou Chi-Hsien, Chuang Lea-Yea, Hong Yi-Ren, Lu Chi-Yu, Chiu Chien-Chih, Chignard Michel
Department of Biochemistry, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Center for Research Resources and Development, Kaohsiung Medical University, Kaohsiung, Taiwan.
Sci Rep. 2016 Aug 9;6:31035. doi: 10.1038/srep31035.
We analyzed a panel of cationic molecules secreted in the culture medium of human respiratory epithelial cells (REC) upon activation by IL-1β and different pathogen-associated molecular patterns. A 9 kDa fragment derived from β2-microglobulin (B2M) was identified and named shed 9 kDa B2M (sB2M-9). The primary structure of sB2M-9 was revealed to increase its pI value that potentially could play an important role in innate defense. sB2M-9 exhibits antibacterial activity against Gram positive Staphylococcus aureus (SA) but not against Gram negative Klebsiella pneumonia (KP). Upon its binding to SA, sB2M-9 induces clumps, a phenomenon not observed with B2M. Migration of THP-1 monocytes exposed to SA clumps was significantly greater than that to SA without clumps. sB2M-9 binds to SA, more likely as a chemokine, to facilitate THP-1 migration. As a whole, we demonstrated that REC release a novel chemokine with antibacterial activity that is shed from B2M to facilitate THP-1 migration.
我们分析了一组在白细胞介素-1β和不同病原体相关分子模式激活下，人呼吸道上皮细胞（REC）培养基中分泌的阳离子分子。鉴定出一个源自β2-微球蛋白（B2M）的9 kDa片段，并将其命名为脱落9 kDa B2M（sB2M-9）。结果显示，sB2M-9的一级结构增加了其pI值，这可能在固有防御中发挥重要作用。sB2M-9对革兰氏阳性金黄色葡萄球菌（SA）具有抗菌活性，但对革兰氏阴性肺炎克雷伯菌（KP）没有抗菌活性。与SA结合后，sB2M-9会诱导聚集，而B2M则不会出现这种现象。暴露于SA聚集体的THP-1单核细胞的迁移明显大于暴露于无聚集体SA的细胞。sB2M-9更有可能作为一种趋化因子与SA结合，以促进THP-1迁移。总体而言我们证明，REC释放一种具有抗菌活性的新型趋化因子，该趋化因子从B2M脱落以促进THP-1迁移。
