title: Expression and functional analyses of liver expressed antimicrobial peptide-2 (LEAP-2) variant forms in human tissues.
abstract: The antimicrobial peptide Liver Expressed Antimicrobial Peptide-2 (LEAP-2) is proposed to function as part of the vertebrate innate immune system. However, the highly conserved nature of the LEAP-2 peptide primary structure among vertebrates suggests more fundamental physiological roles. RT-PCR analyses confirmed expression of LEAP-2 mRNA variants in human gastro-intestinal (GI) epithelial tissues and THP-1 monocytes. Three cDNA products indicative of at least three different spliced transcripts were observed. Translation of the cDNA sequences supported synthesis of transcripts encoding the secreted LEAP-2 peptide and two variants lacking signal sequences suggesting intracellular localisation. The synthesis and cytoplasmic localisation of LEAP-2 peptides in epithelia was supported by immunohistochemical analyses. Functional data suggested that LEAP-2 is not involved in the physiological response of GI epithelia to iron, nor is it mitogenic for epithelial cells or chemotactic for THP-1 monocytes. However, changes in the LEAP-2 transcript patterns associated with the challenge of THP-1 monocytes with lipopolysaccharide (100ng/ml) were supportive of the peptides having multiple roles in the innate immune response.
authors.affiliation: Institute for Cell and Molecular Biosciences, University of Newcastle upon Tyne, UK.
authors.forename: Alison
authors.initials: A
authors.lastname: Howard
authors.forename: Claire
authors.initials: C
authors.lastname: Townes
authors.forename: Panagiota
authors.initials: P
authors.lastname: Milona
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Nile
authors.forename: Giorgios
authors.initials: G
authors.lastname: Michailidis
authors.forename: Judith
authors.initials: J
authors.lastname: Hall
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D001798:Blood Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D049109:Cell Proliferation; D002633:Chemotaxis / Q000502:physiology; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism; D007501:Iron / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008969:Molecular Sequence Data; D009000:Monocytes / Q000166:cytology / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D021382:Protein Sorting Signals / Q000235:genetics; D016415:Sequence Alignment
chemical_list: D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D020033:Protein Isoforms; D021382:Protein Sorting Signals; C475606:liver-expressed antimicrobial peptide 2, human; D007501:Iron