Effect of uromodulin on the bactericidal activities of polymorphonuclear neutrophils

• Main Authors: chen li wei, 陳立偉
• Other Authors: 葉才明
• Format: Others
• Language: zh-TW
• Published: 2000
• Online Access: http://ndltd.ncl.edu.tw/handle/62023090008372309708

碩士 === 國立成功大學 === 微生物暨免疫學研究所 === 88 === 英文摘要 Uromodulin (URO) is the most abundant protein in the urine of pregnant women. However, its physiological function is still unclear. Polymorphonuclear neutrophils (PMNs) are the major phagocytes playing important roles in the innate immunity against bacterial infection. In this study, the effects of URO on the functions of PMN, such as phagocytosis and bactericidal activities, were studied both in human and in the mice. In addition, the mechanism of URO enhancement of bactericidal activity of human PMN by URO was studied. The phagocytosis activities of human PMN were increased after pretreatment with URO (25μg) for 1h in vitro. Furthermore, the bacterial clearance rate against the gram-negative bacteria such as Vibrio vulnificus and Salmonella typhimurium but not gram-positive bacteria such as Staphylococcus aureus and Listeria monocytogenes were increased in URO-pretreated human PMNs. URO pretreatment did not induce TNF-α production and respiratory burst in PMNs as shown by dihydrorhodamaine 123 staining and flow cytometry. However, URO primed human PMN to produce more respiratory burst upon phorbol myristate acetate (PMA) challenge and enhance the binding of fluorescein isothiocyanate-lipopolysaccharide (FITC-LPS) to human PMNs. Not only human PMN, we also found that the bacterial clearance against gram-negative bacteria such as Vibrio vulnificus and Salmonella typhimurium but not gram-positive bacteria such as Staphylococcus aureus and Listeria monocytogenes were increased in mice treated with URO (200μg) 2h before challenge. The percentage and absolute number of PMN from URO-pretreated mice were increased. Furthermore, the phagocytosis activities of PMN from URO-pretreated mice were increased. Collectively, our results suggest that URO can enhance the function of PMN to clear bacterial infection in mice and human, especially against gram-negative bacteria. The results of this study provide us a better understanding of the immunostimulatory effects of URO on PMN and a potential target to develop new immunostimulating agent.