CCL28 Has a Dual Role in Mucosal Immunity as Chemokine with a Broad-Spectrum Antimicrobial Activity

CCL28是一种CC趋化因子，选择性表达于唾液腺、乳腺和结肠。我们发现CCL28是由唾液腺结构性表达和分泌的，对表达CCL28受体OCR10的B220^&lt；low&gt；CD3^-IgA^+浆细胞具有双重趋化作用和作为一种有效的抗菌蛋白。人和小鼠唾液腺浆液性腺泡上皮细胞CCL28呈强阳性，人全唾液和腮腺含高浓度CCL28。我们还注意到人CCL28的C末端区域与人的组蛋白-5序列相似，组蛋白-5是人唾液中的一种富含组氨酸的阳离子多肽，具有很强的杀菌活性。我们证明了人和小鼠CCL28对白色念珠菌、革兰氏阴性菌和革兰氏阳性菌具有广泛的抗菌活性。我们还证明了人CCL28的C末端28个氨基酸结构域具有与组蛋白-5一样的选择性蜡烛状杀菌活性。另一方面，我们没有发现CCL27具有如此强大的抗菌活性，它与CCL28关系最密切，并与CCL28共享CCR10。最后，我们证明了CCL28的抗菌活性对高盐浓度很敏感，与大多数其他抗菌肽一样，在扫描电子显微镜下显示出对靶微生物膜通透性的快速诱导。结论：CCL28在粘膜免疫中具有化学诱导剂和具有较强抗菌活性的分泌型分子的双重作用

CCL28 is a CC chemokine selectively expressed in the salivary glands, mammary glands and colon. We found that CCL28 is constitutively expressed and secreted by the salivary glands and has a dual role as a chemoattractant for B220^<low>CD3^-IgA^+ plasma cells expressing OCR10, receptor for CCL28, and as a potent antimicrobial protein. Serous acinar epithelial cells of human and mouse salivary glands were strongly positive for CCL28 and human whole and parotid saliva contained CCL28 at high concentrations. We also noticed a sequence similarity between the C-terminal region of human CCL28 and human histatin-5, a histidine-rich cationic peptide in human saliva with a potent candidacidal activity. We demonstrated that human and mouse CCL28 had a broad spectrum of antimicrobial activity against Candida albicans, Gram-negative bacteria and Gram-positive bacteria We also demonstrated that the C-terminal 28-amino acid domain of human CCL28 has a selective candklacidal activity as histatin-5. On the other hand, we found no such potent antimicrobial activity with CCL27, which is most closely related to CCL28 and shares CCR10 with CCL28. Finally, we demonstrated that the antimicrobial activity of CCL28 is sensitive to high salt concentrations, as with most other antimicrobial peptides, and displays a rapid induction of membrane permeability in target microbes under scanning electron microscopy In conclusion, CCL28 has a dual role in mucosal immunity as a chemoattractant and as a secreted molecule with a potent antimicrobial activity