Hagiwara Koichi, Kikuchi Tohru, Endo Yoshiyuki, Usui Kazuhiro, Takahashi Mitsu, Shibata Naoko, Kusakabe Takashi, Xin Hong, Hoshi Sachiko, Miki Makoto, Inooka Nozomu, Tokue Yutaka, Nukiwa Toshihiro
Department of Respiratory Oncology and Molecular Medicine, Division of Cancer Control, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
J Immunol. 2003 Feb 15;170(4):1973-9. doi: 10.4049/jimmunol.170.4.1973.
Antibacterial proteins are important participants in the innate immunity system. Elafin and SLPI are the whey acidic protein (WAP) motif proteins with both antibacterial activity and antiprotease activity, and their role in innate immunity is under intense investigation. We cloned two novel antibacterial WAP motif proteins from mice, SWAM1 and SWAM2. SWAM1 and SWAM2 are composed of a signal sequence and a single WAP motif that has high homologies with the WAP motifs of elafin and SLPI. SWAM1 is constitutively expressed in kidney and epididymis, and is induced in the pneumonic lung. SWAM2 is constitutively expressed in tongue. SWAM1 and SWAM2 inhibit the growth of both Escherichia coli and Staphylococcus aureus at a IC(90) (concentration that achieves 90% inhibition) of 10 microM. Human genes LOC149709 and huWAP2 are considered to be human SWAM1 and SWAM2, respectively. These and several WAP motif proteins (WAP1, elafin, SLPI, HE4, eppin, C20orf170, LOC164237, and WFDC3) form a gene cluster on human chromosome 20, suggesting that they may be derived from the same ancestral gene by gene duplication. Our results underscore the role of the WAP motif as a skeletal motif to form antibacterial proteins, and warrant the study of antibacterial activity in other WAP motif proteins.
抗菌蛋白是天然免疫系统的重要参与者。弹性蛋白酶抑制因子（Elafin）和分泌性白细胞蛋白酶抑制因子（SLPI）是具有抗菌活性和抗蛋白酶活性的乳清酸性蛋白（WAP）基序蛋白，它们在天然免疫中的作用正在深入研究中。我们从小鼠中克隆了两种新型抗菌WAP基序蛋白，即SWAM1和SWAM2。SWAM1和SWAM2由一个信号序列和一个与Elafin和SLPI的WAP基序具有高度同源性的单一WAP基序组成。SWAM1在肾脏和附睾中组成性表达，并在肺炎肺组织中被诱导表达。SWAM2在舌头中组成性表达。SWAM1和SWAM2在10微摩尔的IC（90）（达到90%抑制的浓度）下抑制大肠杆菌和金黄色葡萄球菌的生长。人类基因LOC149709和huWAP2分别被认为是人类的SWAM1和SWAM2。这些以及几种WAP基序蛋白（WAP1、Elafin、SLPI、HE4、附睾分泌蛋白（eppin）、C20orf170、LOC164237和WFDC3）在人类20号染色体上形成一个基因簇，这表明它们可能通过基因复制来源于同一个祖先基因。我们的结果强调了WAP基序作为形成抗菌蛋白的骨架基序的作用，并保证了对其他WAP基序蛋白抗菌活性的研究。
