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Infection and Immunity, January 2005, p. 583-591, Vol. 73, No. 1
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.1.583-591.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Interaction and Cellular Localization of the Human Host Defense Peptide LL-37 with Lung Epithelial Cells

Y. Elaine Lau,1 Annett Rozek,2 Monisha G. Scott,1,2 Danika L. Goosney,1,2 Donald J. Davidson,3 and Robert E. W. Hancock1*

Department of Microbiology and Immunology, University of British Columbia,1 Inimex Pharmaceuticals Inc.,2 B.C. Research Institute for Children's and Women's Health, Vancouver, British Columbia, Canada3

Received 19 August 2004/ Accepted 4 September 2004

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.

* Corresponding author. Mailing address: The Department of Microbiology and Immunology, University of British Columbia, 6174 University Blvd., Vancouver, British Columbia, Canada, V6T 1Z3. Phone: (604) 822-2682. Fax: (604) 822-6041. E-mail: bob{at}cmdr.ubc.ca.

Editor: V. J. DiRita

Infection and Immunity, January 2005, p. 583-591, Vol. 73, No. 1
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.1.583-591.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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