title: A cathelicidin family of human antibacterial peptide LL-37 induces mast cell chemotaxis.
abstract: The mast cell is one of the major effector cells in inflammatory reactions and can be found in most tissues throughout the body. During inflammation, an increase in the number of mast cells in the local milieu occurs, and such accumulation requires directed migration of this cell population. As it has previously been reported that the human cathelicidin-derived antibacterial peptide, LL-37, stimulates the degranulation of mast cells, we hypothesized that LL-37 could be a mast cell chemotaxin. The present study shows that LL-37 is a potent chemotactic factor for mast cells. The chemotactic response was dose-dependent and bell-shaped, reaching an optimal concentration of 5 microg/ml. In addition, checkerboard analysis showed that cell migration towards this peptide was chemotactic rather than chemokinetic. Moreover, Scatchard analysis using 125I-labelled LL-37-derived peptide revealed that LL-37 has at least two classes of receptors, namely high- and low-affinity receptors, on mast cells. Furthermore, the competitive binding assay suggested that LL-37 is unlikely to utilize formyl peptide receptor-like 1 (FPRL1), a functional LL-37 receptor for neutrophil and monocyte migration, on mast cells. In addition, the treatment of cells with pertussis toxin and phospholipase C inhibitor, U-73122, inhibited LL-37-mediated migration, indicating that LL-37 induces mast cell chemotaxis through a Gi protein-phospholipase C signalling pathway. These results show that besides its antibacterial activities, LL-37 may have the potential to recruit mast cells to inflammation foci.
authors.affiliation: Department of Biochemistry, Juntendo University, School of Medicine, Tokyo, Japan.
authors.forename: François
authors.initials: F
authors.lastname: Niyonsaba
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Iwabuchi
authors.forename: Akimasa
authors.initials: A
authors.lastname: Someya
authors.forename: Michimasa
authors.initials: M
authors.lastname: Hirata
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Matsuda
authors.forename: Hideoki
authors.initials: H
authors.lastname: Ogawa
authors.forename: Isao
authors.initials: I
authors.lastname: Nagaoka
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000276:immunology*; D001667:Binding, Competitive / Q000276:immunology; D002118:Calcium / Q000378:metabolism; D054804:Cathelicidins; D002630:Chemotactic Factors / Q000276:immunology*; D002633:Chemotaxis / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D004963:Estrenes; D007106:Immune Sera / Q000276:immunology; D008297:Male; D008407:Mast Cells / Q000276:immunology* / Q000378:metabolism; D037342:Pertussis Toxin; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011355:Prodrugs / Q000494:pharmacology*; D011760:Pyrrolidinones; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000276:immunology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins; D002630:Chemotactic Factors; D004963:Estrenes; D007106:Immune Sera; D010726:Phosphodiesterase Inhibitors; D011355:Prodrugs; D011760:Pyrrolidinones; D010566:Virulence Factors, Bordetella; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D037342:Pertussis Toxin; D002118:Calcium