L-ficolin, one of lectin families, is a recently identified complement factor that initiates lectin pathway of complement. Little is known about its role in viral hepatitis. In the present study, we found that L-ficol...L-ficolin, one of lectin families, is a recently identified complement factor that initiates lectin pathway of complement. Little is known about its role in viral hepatitis. In the present study, we found that L-ficolin in serum from 103 patients with hepatitis C virus （HCV）, were significantly higher than that in 150 healthy controls. We further found that L-ficolin expressions were significantly increased in vitro study by HCV JFH-1 infected human hepatocyte cell line Huh7.5.1. Investigation of the mechanisms of the L-ficolin action on HCV demonstrated that L-ficolin protein could recognize and bind to envelope glycoproteins E1 and E2 of HCV, activating the lectin complement pathway-mediated cytolytic activity in HCV-infected hepatocyte. This interaction between L-ficolin and HCV E1 and E2 glycoproteins was attributed to the N-glycans of E1 and E2. These findings provide new insights into the biological functions of L-ficolin in clinically important hepatic viral diseases.展开更多
Ficolins are serum complement lectins,with a structure similar to mannose-binding lectin （MBL） and lung surfactant protein （SP）-A and SP-D.Ficolins activate the lectin complement system and play important roles in...Ficolins are serum complement lectins,with a structure similar to mannose-binding lectin （MBL） and lung surfactant protein （SP）-A and SP-D.Ficolins activate the lectin complement system and play important roles in host innate immunity.Ficolins are members of the collectin family of proteins,which act as pattern recognition receptors （PRRs）.They are soluble oligomeric defense proteins with lectin-like activity,and are able to recognize pathogen-associated molecular patterns （PAMPs）,which are carbohydrate molecules on the surface of pathogens,and of apoptotic,necrotic,and malignant cells.Upon binding to their specific PAMPs,ficolins may trigger activation of the immune system either （1） by initiating activation of complement via the lectin pathway,（2） by a primitive type of opsonophagocytosis,or （3） by stimulating secretion of the inflammatory cytokines interferon （IFN）-γ,interleukin （IL）-17,IL-6,and tumor necrosis factor （TNF）-α,and production of nitric oxide （NO）by macrophages,thus limiting the infection and concurrently orchestrating the subsequent adaptive immune response.Recently,a number of reports have shown that dysfunction or abnormal expression of ficolins may play crucial roles in viral and bacterial diseases and in inflammation.This review summarizes the reports on the roles of ficolins in the infectious diseases,and provides insight into ficolins as novel innate immune therapeutic options to treat these diseases.展开更多
基金Acknowledgments This work was supported by grants to X.-L. Zhang from the National Natural Science Foundation of China （30870122, 30670098 and 20532020）, 973 Program of China 2006CB 504300 and 2009CB522507, National Grand Program on Key Infectious Disease （2008ZX10003-005）, Hubei Province Science Technology Department （2006ABD007, 2007ABC 010） and Hubei Ministry of Public Health of （JX1B074）.
文摘L-ficolin, one of lectin families, is a recently identified complement factor that initiates lectin pathway of complement. Little is known about its role in viral hepatitis. In the present study, we found that L-ficolin in serum from 103 patients with hepatitis C virus （HCV）, were significantly higher than that in 150 healthy controls. We further found that L-ficolin expressions were significantly increased in vitro study by HCV JFH-1 infected human hepatocyte cell line Huh7.5.1. Investigation of the mechanisms of the L-ficolin action on HCV demonstrated that L-ficolin protein could recognize and bind to envelope glycoproteins E1 and E2 of HCV, activating the lectin complement pathway-mediated cytolytic activity in HCV-infected hepatocyte. This interaction between L-ficolin and HCV E1 and E2 glycoproteins was attributed to the N-glycans of E1 and E2. These findings provide new insights into the biological functions of L-ficolin in clinically important hepatic viral diseases.
基金supported by grants from the National Outstanding Youth Foundation of China(81025008)973 Program of China(2012CB720604)+4 种基金National Natural Science Foundation of China(31221061,31370197)National Grand Program on Key Infectious Disease(2012ZX10003002-015)the Hubei Province's Outstanding Medical Academic Leader Program,Changjiang Scholars and Innovative Research Team,the 211 program(303-581045)the Science and Technology Program of Wuhan(301274075)the FundamentalResearch Funds for the Central Universities
文摘Ficolins are serum complement lectins,with a structure similar to mannose-binding lectin （MBL） and lung surfactant protein （SP）-A and SP-D.Ficolins activate the lectin complement system and play important roles in host innate immunity.Ficolins are members of the collectin family of proteins,which act as pattern recognition receptors （PRRs）.They are soluble oligomeric defense proteins with lectin-like activity,and are able to recognize pathogen-associated molecular patterns （PAMPs）,which are carbohydrate molecules on the surface of pathogens,and of apoptotic,necrotic,and malignant cells.Upon binding to their specific PAMPs,ficolins may trigger activation of the immune system either （1） by initiating activation of complement via the lectin pathway,（2） by a primitive type of opsonophagocytosis,or （3） by stimulating secretion of the inflammatory cytokines interferon （IFN）-γ,interleukin （IL）-17,IL-6,and tumor necrosis factor （TNF）-α,and production of nitric oxide （NO）by macrophages,thus limiting the infection and concurrently orchestrating the subsequent adaptive immune response.Recently,a number of reports have shown that dysfunction or abnormal expression of ficolins may play crucial roles in viral and bacterial diseases and in inflammation.This review summarizes the reports on the roles of ficolins in the infectious diseases,and provides insight into ficolins as novel innate immune therapeutic options to treat these diseases.
