Pleurocidin, a novel antimicrobial peptide, induces human mast cell activation through the FPRL1 receptor

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DOIResolve DOI: http://doi.org/10.1038/mi.2013.37
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TypeArticle
Journal titleMucosal Immunology
ISSN1933-0219
Volume7
Issue1
Pages177187; # of pages: 11
AbstractPleurocidins 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 Ca2+ 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. © 2014 Society for Mucosal Immunology.
Publication date
LanguageEnglish
AffiliationNational Research Council Canada; Security and Disruptive Technologies; Aquatic and Crop Resource Development; Human Health Therapeutics
Peer reviewedYes
NRC number55943
NPARC number21270785
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Record identifier1afa80d2-0481-4c5a-8cef-6f252b405d64
Record created2014-02-17
Record modified2016-05-09
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