Human β-defensin-1:: An antimicrobial peptide of urogenital tissues
Human β-defensin-1:: An antimicrobial peptide of urogenital tissues
复制标题
DOI：
10.1172/jci1861
复制
发表时间：
1998-04-15
影响因子：
15.9
通讯作者：
Ganz, T
中科院分区：
文献类型：
--
作者：
Valore, EV;Park, CH;Ganz, T
抗菌肽是广泛存在于动植物体内的天然宿主防御介质。一种由36个氨基酸组成的抗微生物肽，被命名为人β -防御素-1 (HBD-1)，最近从血液透析液中纯化出来，但其组织来源尚未确定。通过Northern blotting，我们发现肾脏和女性生殖道中HBD-1 mRNA的浓度最高。原位杂交将HBD-1 mRNA定位在女性生殖道的肾袢、远端小管、集管的上皮层以及阴道、宫颈外、宫颈内、子宫和输卵管的上皮层。使用一种新的技术来检测尿液中的阳离子肽，我们恢复了几种形式的HBD-1，长度从36到47个氨基酸（aa）残基不等，并且通过氨基末端截断而彼此不同。估计尿中HBD-1形式的总浓度为10-100 μ g/l， HBD-1肽的总量和HBD-1形式的相对比例存在个体差异。在血浆中也发现了多种形式的HBD-1（大小36- 47aa），它们与酸性条件下释放肽的载体大分子结合，并存在于阴道粘膜分泌物中（39,40和44aa）。通过免疫染色，HBD-1位于Henle袢的肾腔内，但在肾脏或女性生殖组织中未发现细胞内储存位点。重组HBD-1形式（36、39和42 aa）和天然HBD-1形式在微摩尔浓度下对实验室和临床大肠杆菌菌株具有抗菌作用。低pH条件下HBD-1活性变化不明显，但高盐条件下HBD-1活性受到抑制。一些HBD-1肽在未浓缩（低电导）尿液中仍保持对大肠杆菌的活性，而36aa形式即使在正常（高电导）尿液中也具有杀微生物作用。尿生殖道中HBD-1的产生可能有助于局部抗菌防御。
Antimicrobial peptides are widely distributed mediators of innate host defense in animals and plants. A 36 amino acid antimicrobial peptide belonging to the defensin family, and named human beta-defensin-1 (HBD-1), was purified recently from hemodialysate fluid, but its tissue sources were not identified. By Northern blotting, we found the highest concentrations of HBD-1 mRNA in the kidney and the female reproductive tract. In situ hybridization localized the HBD-1 mRNA in the epithelial layers of the loops of Henle, distal tubules, and the collecting ducts of the kidney and the epithelial layers of the vagina, ectocervix, endocervix, uterus, and fallopian tubes in the female reproductive tract. Using a novel technique designed to detect cationic peptides in urine, we recovered several forms of HBD-1 ranging in length from 36 to 47 amino acid (aa) residues and differing from each other by amino terminal truncation. The total concentration of HBD-1 forms in voided urine was estimated at 10-100 mu g/liter, with individual variations in the total amount of HBD-1 peptides and the relative proportion of HBD-1 forms. Multiple forms of HBD-1 (size 36-47 aa) were also found in the blood plasma, bound to carrier macromolecules that released the peptide under acid conditions, and in vaginal mucosal secretions (39, 40, and 44 aa). By immunostaining, HBD-1 was located in the kidney within the lumen of the loops of Henle, but no intracellular storage sites were identified in renal or female reproductive tissues. Recombinant HBD-1 forms (36, 39, and 42 aa) and natural HBD-1 forms were antimicrobial to laboratory and clinical strains of Escherichia coli at micromolar concentrations. HBD-1 activity was not changed appreciably by low pH, but was inhibited by high salt conditions. Some of the HBD-1 peptides retained their activity against E. coli in unconcentrated (low conductance) urine, and the 36 aa form was microbicidal even in normal (high conductance) urine. Production of HBD-1 in the urogenital tract could contribute to local antimicrobial defense.