Interaction and cellular localization of the human host defense peptide LL-37 with lung epithelial cells.
LL-37 is a human cationic host defense peptide that is an essential component of innate immunity. In addition to its modest antimicrobial activity, LL-37 affects the gene expression and behavior of effector cells involved in the innate immune response, although its mode of interaction with eukaryotic cells remains unclear. The interaction of LL-37 with epithelial cells was characterized in tissue culture by using biotinylated LL-37 and confocal microscopy. It was demonstrated that LL-37 was actively taken up into A549 epithelial cells and eventually localized to the perinuclear region. Specific inhibitors were used to demonstrate that the uptake process was not mediated by actin but required elements normally involved in endocytosis and that trafficking to the perinuclear region was dependent on microtubules. By using nonlinear regression analysis, it was revealed that A549 epithelial cells have two receptors for LL-37B, with high and low affinity for LL-37, respectively. These results indicate the mode of interaction of LL-37 with epithelial cells and further our understanding of its role in modulating the innate immune response.
Lau
Y Elaine
YE
The Department of Microbiology and Immunology, University of British Columbia, 6174 University Blvd., Vancouver, British Columbia, Canada.
Rozek
Annett
A
Scott
Monisha G
MG
Goosney
Danika L
DL
Davidson
Donald J
DJ
Hancock
Robert E W
RE
D000595:Amino Acid Sequence; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000493:pharmacokinetics*; D019921:Biotinylation; D002460:Cell Line; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D008168:Lung / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D044042:Receptors, Formyl Peptide / Q000502:physiology; D043562:Receptors, G-Protein-Coupled / Q000502:physiology; D044067:Receptors, Lipoxin / Q000502:physiology; D054804:Cathelicidins
D023181:Antimicrobial Cationic Peptides; C105101:FPR2 protein, human; D044042:Receptors, Formyl Peptide; D043562:Receptors, G-Protein-Coupled; D044067:Receptors, Lipoxin; D054804:Cathelicidins