Extra-hepatic transcription of the human mannose-binding lectin gene (mbl2) and the MBL-associated serine protease 1-3 genes.
Mannose-binding lectin (MBL) is a part of the innate immune defense and activates complement via MBL associated serine proteases (MASPs). Human MBL is expressed by hepatocytes, but recent evidence in mice indicates a substantial extra-hepatic transcription. Therefore, we investigated whether mRNA transcribed from the human mbl2 gene as well as the masp genes was present in different tissues. The transcription of human mbl2 is regulated by two alternative promoters (named 0 and 1) where promoter 0 derived transcripts include an additional 5' untranslated part encoded by an extra exon (exon 0). Low extra-hepatic levels of mbl2 mRNA were predominantly found in small intestine and testis tissue, and were quantitatively dominated by promoter 1 transcripts. Moreover, these transcripts varied due to the use of alternative acceptor splice sites positioned inside exon 1. The mRNA distribution of masp1 and masp2 were found very similar to that of mbl2, while masp3 mRNA seemed ubiquitous present at quite high levels when compared to liver. These results indicate that the regulation of mbl2 gene expression in man is more complex than previously anticipated and that local expression of MBL may be relevant in local immune defense, particularly in restricted areas of the gastrointestinal and reproductive tracts.
Seyfarth
Jeanette
J
Tissue Typing Laboratory-7631, Department of Clinical Immunology, Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen Ø, Denmark.
Garred
Peter
P
Madsen
Hans O
HO
D017398:Alternative Splicing; D000818:Animals; D001483:Base Sequence; D005312:Fetal Blood / Q000166:cytology; D005786:Gene Expression Regulation; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000737:chemistry / Q000378:metabolism*; D037601:Mannose-Binding Lectin / Q000032:analysis / Q000235:genetics*; D037241:Mannose-Binding Lectins / Q000235:genetics*; D050606:Mannose-Binding Protein-Associated Serine Proteases / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D009000:Monocytes / Q000737:chemistry / Q000187:drug effects; D011401:Promoter Regions, Genetic; D022821:RNA Splice Sites; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D014018:Tissue Distribution; D014158:Transcription, Genetic
D008070:Lipopolysaccharides; C445619:MBL2 protein, human; D037601:Mannose-Binding Lectin; D037241:Mannose-Binding Lectins; D022821:RNA Splice Sites; D012333:RNA, Messenger; C084067:MASP1 protein, human; C105296:MASP2 protein, human; D050606:Mannose-Binding Protein-Associated Serine Proteases