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Defective activities, but not secretions, resulting from gene point mutations of human mannan-binding lectin
Human mannan-binding lectin (MBL) plays a pivotal role in innate immunity. Substantial literature supports the belief that three point mutations, CGT52TGT, GGC54GAC and GGA57GAA, in the collagen-like region (CLR) of the human MBL gene, are associated with increased susceptibility to infection, autoi...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3493102/ https://www.ncbi.nlm.nih.gov/pubmed/22323042 http://dx.doi.org/10.3892/mmr.2012.782 |
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author | LIU, YING LIU, FENG-LING BAI, ZHI-JUN ZHAO, NA ZHANG, LI-YUN LU, XIAO CHEN, ZHENG-LIANG |
author_facet | LIU, YING LIU, FENG-LING BAI, ZHI-JUN ZHAO, NA ZHANG, LI-YUN LU, XIAO CHEN, ZHENG-LIANG |
author_sort | LIU, YING |
collection | PubMed |
description | Human mannan-binding lectin (MBL) plays a pivotal role in innate immunity. Substantial literature supports the belief that three point mutations, CGT52TGT, GGC54GAC and GGA57GAA, in the collagen-like region (CLR) of the human MBL gene, are associated with increased susceptibility to infection, autoimmunity and carcinogenesis. To investigate the mechanisms of MBL deficiency, human wild-type and three variant MBL genes were expressed in COS-7 and Chinese hamster ovary (CHO) cells. Results showed that no apparent differences were found among the levels of gene transcription and protein secretion of four forms of MBL. However, the degree of oligomerization of variant forms of MBL was found to be much lower than that of recombinant human wild-type MBL. The ability of variant MBL proteins to bind mannan was much weaker than that of the wild-type MBL protein, and the MBL variants failed to effectively activate the complement lectin pathway. These data suggested that a lower order oligomer, but not decreased plasma levels of MBL, may be the main result of MBL gene mutations and may be associated with immunodeficiency. |
format | Online Article Text |
id | pubmed-3493102 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-34931022013-04-01 Defective activities, but not secretions, resulting from gene point mutations of human mannan-binding lectin LIU, YING LIU, FENG-LING BAI, ZHI-JUN ZHAO, NA ZHANG, LI-YUN LU, XIAO CHEN, ZHENG-LIANG Mol Med Rep Article Human mannan-binding lectin (MBL) plays a pivotal role in innate immunity. Substantial literature supports the belief that three point mutations, CGT52TGT, GGC54GAC and GGA57GAA, in the collagen-like region (CLR) of the human MBL gene, are associated with increased susceptibility to infection, autoimmunity and carcinogenesis. To investigate the mechanisms of MBL deficiency, human wild-type and three variant MBL genes were expressed in COS-7 and Chinese hamster ovary (CHO) cells. Results showed that no apparent differences were found among the levels of gene transcription and protein secretion of four forms of MBL. However, the degree of oligomerization of variant forms of MBL was found to be much lower than that of recombinant human wild-type MBL. The ability of variant MBL proteins to bind mannan was much weaker than that of the wild-type MBL protein, and the MBL variants failed to effectively activate the complement lectin pathway. These data suggested that a lower order oligomer, but not decreased plasma levels of MBL, may be the main result of MBL gene mutations and may be associated with immunodeficiency. D.A. Spandidos 2012-02-06 2012-04 /pmc/articles/PMC3493102/ /pubmed/22323042 http://dx.doi.org/10.3892/mmr.2012.782 Text en Copyright © 2012, Spandidos Publications |
spellingShingle | Article LIU, YING LIU, FENG-LING BAI, ZHI-JUN ZHAO, NA ZHANG, LI-YUN LU, XIAO CHEN, ZHENG-LIANG Defective activities, but not secretions, resulting from gene point mutations of human mannan-binding lectin |
title | Defective activities, but not secretions, resulting from gene point mutations of human mannan-binding lectin |
title_full | Defective activities, but not secretions, resulting from gene point mutations of human mannan-binding lectin |
title_fullStr | Defective activities, but not secretions, resulting from gene point mutations of human mannan-binding lectin |
title_full_unstemmed | Defective activities, but not secretions, resulting from gene point mutations of human mannan-binding lectin |
title_short | Defective activities, but not secretions, resulting from gene point mutations of human mannan-binding lectin |
title_sort | defective activities, but not secretions, resulting from gene point mutations of human mannan-binding lectin |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3493102/ https://www.ncbi.nlm.nih.gov/pubmed/22323042 http://dx.doi.org/10.3892/mmr.2012.782 |
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