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, 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.
Department of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, PR China.
Ying
Y
Liu
Feng-Ling
FL
Liu
Zhi-Jun
ZJ
Bai
Na
N
Zhao
Li-Yun
LY
Zhang
Xiao
X
Lu
Zheng-Liang
ZL
Chen
D000818:Animals; D016466:CHO Cells; D019556:COS Cells; D002522:Chlorocebus aethiops; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D008358:Mannose / Q000378:metabolism*; D037601:Mannose-Binding Lectin / Q000235:genetics* / Q000378:metabolism*; D017354:Point Mutation; D011485:Protein Binding; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism
D037601:Mannose-Binding Lectin; D011994:Recombinant Proteins; D008358:Mannose