title: Pleurocidin, a novel antimicrobial peptide, induces human mast cell activation through the FPRL1 receptor.
abstract: Pleurocidins are a novel family of α-helical cationic antimicrobial peptides (CAPs) that are structurally and functionally similar to cathelicidins, one of the major CAP families. As cathelicidins stimulate mast cell chemotaxis and mediator release, we postulated that pleurocidins similarly activate mast cells. A screen of 20 pleurocidin peptides revealed that some were capable of degranulating the human mast cell line LAD2 (Laboratory of Allergic Diseases 2). Pleurocidin NRC-04 caused LAD2 to adhere, migrate, degranulate, and release cysteinyl leukotrienes and prostaglandin D2. Moreover, pleurocidin increased intracellular Ca(2+) mobilization in mast cells and induced the production of proinflammatory chemokines such as monocyte chemotactic protein-1/C-C motif chemokine ligand 2 (CCL2) and macrophage inflammatory protein-1β/CCL4. Our evaluation of possible cellular mechanisms suggested that G proteins, phosphoinositol-3 kinase (PI3K), phospholipase C (PLC), and phosphokinase C (PKC) were involved in pleurocidin-induced mast cell activation as evidenced by the inhibitory effects of pertussis toxin (G protein inhibitor), wortmanin (PI3K inhibitor), U-73122 (PLC inhibitor), and Ro-31-8220 (PKC inhibitor), respectively. We also found that human mast cells expressed the N-formyl-peptide receptor 1 (FPRL1) receptor and FPRL1-specific inhibitor affected pleurocidin-mediated activation of mast cell. Our finding that the novel CAP pleurocidin activated human mast cell through G protein-coupled receptor signaling suggests that this peptide might have immunomodulatory functions.
authors.affiliation: 1] National Research Council, Charlottetown, Prince Edward Island, Canada [2] Department of Biomedical Sciences, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, Prince Edward Island, Canada.
authors.forename: P
authors.initials: P
authors.lastname: Pundir
authors.affiliation: National Research Council, Charlottetown, Prince Edward Island, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Catalli
authors.affiliation: National Research Council, Halifax, Nova Scotia, Canada.
authors.forename: C
authors.initials: C
authors.lastname: Leggiadro
authors.affiliation: National Research Council, Halifax, Nova Scotia, Canada.
authors.forename: S E
authors.initials: SE
authors.lastname: Douglas
authors.affiliation: 1] National Research Council, Charlottetown, Prince Edward Island, Canada [2] National Research Council, Edmonton, Alberta, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Kulka
mesh_terms: D000595:Amino Acid Sequence; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects / Q000276:immunology; D015550:Cell Degranulation / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D018925:Chemokines / Q000235:genetics; D002633:Chemotaxis / Q000187:drug effects / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D029941:Fish Proteins / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D008969:Molecular Sequence Data; D044042:Receptors, Formyl Peptide / Q000235:genetics / Q000378:metabolism*; D044067:Receptors, Lipoxin / Q000235:genetics / Q000378:metabolism*; D058486:Receptors, Purinergic P2X7 / Q000235:genetics / Q000378:metabolism; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D023181:Antimicrobial Cationic Peptides; D018925:Chemokines; C105101:FPR2 protein, human; D029941:Fish Proteins; D044042:Receptors, Formyl Peptide; D044067:Receptors, Lipoxin; D058486:Receptors, Purinergic P2X7; C105851:pleurocidin; D002118:Calcium