Cathelicidin LL-37 increases lung epithelial cell stiffness, decreases transepithelial permeability, and prevents epithelial invasion by Pseudomonas aeruginosa

Journal of Immunology

Volumn 187, Issue 12, 2011, Pages 6402-6409

  Byfield, Fitzroy J ^a   Kowalski, Marek ^a   Cruz, Katrina ^a   Leszczyńska, Katarzyna ^b   Namiot, Andrzej ^b   Savage, Paul B ^c   Bucki, Robert ^a   Janmey, Paul A ^a  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

^b MEDICAL UNIVERSITY OF BIALYSTOK   (Poland)

^c Brigham Young University   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIINFECTIVE AGENT; BACTERIUM LIPOPOLYSACCHARIDE; CATHELICIDIN ANTIMICROBIAL PEPTIDE LL 37; CSA 13; F ACTIN; FLUORESCEIN ISOTHIOCYANATE DEXTRAN; GENTAMICIN; KR 20 PEPTIDE; PHALLOIDIN; RK 31 PEPTIDE; SPHINGOSINE 1 PHOSPHATE; UNCLASSIFIED DRUG; WLBU2 PEPTIDE;

ACTIN POLYMERIZATION; ANTIBACTERIAL ACTIVITY; ARTICLE; ATOMIC FORCE MICROSCOPY; BACTERIAL GROWTH; BACTERICIDAL ACTIVITY; BRONCHIAL EPITHELIAL CELL; CELL INVASION; CELL STIFFNESS; CONCENTRATION RESPONSE; CONTROLLED STUDY; EPITHELIUM CELL; HUMAN; HUMAN CELL; INTERNALIZATION; LUNG EPITHELIAL CELL; MEMBRANE PERMEABILITY; NONHUMAN; PRIORITY JOURNAL; PSEUDOMONAS AERUGINOSA; TRANSEPITHELIAL PERMEABILITY; YOUNG MODULUS;

AMINO ACID SEQUENCE; ANTIMICROBIAL CATIONIC PEPTIDES; CATHELICIDINS; CELL LINE, TUMOR; CELL MEMBRANE PERMEABILITY; CELL MIGRATION INHIBITION; CELLS, CULTURED; HUMANS; LUNG; MOLECULAR SEQUENCE DATA; PSEUDOMONAS AERUGINOSA; RESPIRATORY MUCOSA;

EID: 83755183848     PISSN: 00221767     EISSN: 15506606     Source Type: Journal    
DOI: 10.4049/jimmunol.1102185     Document Type: Article

References (57)

1. Yeaman, M. R., and N. Y. Yount. 2003. Mechanisms of antimicrobial peptide action and resistance. Pharmacol. Rev. 55: 27-55. (Pubitemid 36268398)
2. Jenssen, H., P. Hamill, and R. E. Hancock. 2006. Peptide antimicrobial agents. Clin. Microbiol. Rev. 19: 491-511. (Pubitemid 44137212)
3. Bucki, R., K. Leszczyńska, A. Namiot, and W. Sokołowski. 2010. Cathelicidin LL-37: a multitask antimicrobial peptide. Arch. Immunol. Ther. Exp. (Warsz.) 58: 15-25.
4. Gudmundsson, G. H., B. Agerberth, J. Odeberg, T. Bergman, B. Olsson, and R. Salcedo. 1996. The human gene FALL39 and processing of the cathelin precursor to the antibacterial peptide LL-37 in granulocytes. Eur. J. Biochem. 238: 325-332. (Pubitemid 26188246)
5. Pütsep, K., G. Carlsson, H. G. Boman, and M. Andersson. 2002. Deficiency of antibacterial peptides in patients with morbus Kostmann: an observation study. Lancet 360: 1144-1149. (Pubitemid 35246490)
6. Nizet, V., T. Ohtake, X. Lauth, J. Trowbridge, J. Rudisill, R. A. Dorschner, V. Pestonjamasp, J. Piraino, K. Huttner, and R. L. Gallo. 2001. Innate antimicrobial peptide protects the skin from invasive bacterial infection. Nature 414: 454-457. (Pubitemid 34173727)
7. Bals, R., D. J. Weiner, R. L. Meegalla, and J. M. Wilson. 1999. Transfer of a cathelicidin peptide antibiotic gene restores bacterial killing in a cystic fibrosis xenograft model. J. Clin. Invest. 103: 1113-1117. (Pubitemid 29207244)
8. De Yang, Q., A. P. Chen, G. M. Schmidt, J. M. Anderson, J. Wang, J. J. Wooters, Oppenheim, and O. Chertov. 2000. LL-37, the neutrophil granule- and epithelial cell-derived cathelicidin, utilizes formyl peptide receptor-like 1 (FPRL1) as a receptor to chemoattract human peripheral blood neutrophils, monocytes, and T cells. J. Exp. Med. 192: 1069-1074.
9. Tjabringa, G. S., J. Aarbiou, D. K. Ninaber, J. W. Drijfhout, O. E. Sørensen, N. Borregaard, K. F. Rabe, and P. S. Hiemstra. 2003. The antimicrobial peptide LL-37 activates innate immunity at the airway epithelial surface by transactivation of the epidermal growth factor receptor. J. Immunol. 171: 6690-6696. (Pubitemid 37532101)
10. Shaykhiev, R., C. Beisswenger, K. Kändler, J. Senske, A. Püchner, T. Damm, J. Behr, and R. Bals. 2005. Human endogenous antibiotic LL-37 stimulates airway epithelial cell proliferation and wound closure. Am. J. Physiol. Lung Cell. Mol. Physiol. 289: L842-L848. (Pubitemid 41504416)
11. Elssner, A., M. Duncan, M. Gavrilin, and M. D. Wewers. 2004. A novel P2X7 receptor activator, the human cathelicidin-derived peptide LL37, induces IL-1 beta processing and release. J. Immunol. 172: 4987-4994. (Pubitemid 38456425)
12. Bowdish, D. M., D. J. Davidson, Y. E. Lau, K. Lee, M. G. Scott, and R. E. Hancock. 2005. Impact of LL-37 on anti-infective immunity. J. Leukoc. Biol. 77: 451-459. (Pubitemid 40489520)
13. Ciornei, C. D., T. Sigurdardóttir, A. Schmidtchen, and M. Bodelsson. 2005. Antimicrobial and chemoattractant activity, lipopolysaccharide neutralization, cytotoxicity, and inhibition by serum of analogs of human cathelicidin LL-37. Antimicrob. Agents Chemother. 49: 2845-2850. (Pubitemid 40917601)
14. Pier, G. B., M. Grout, T. S. Zaidi, J. C. Olsen, L. G. Johnson, J. R. Yankaskas, and J. B. Goldberg. 1996. Role of mutant CFTR in hypersusceptibility of cystic fibrosis patients to lung infections. Science 271: 64-67. (Pubitemid 26033276)
15. Lee, A., D. Chow, B. Haus, W. Tseng, D. Evans, S. Fleiszig, G. Chandy, and T. Machen. 1999. Airway epithelial tight junctions and binding and cytotoxicity of Pseudomonas aeruginosa. Am. J. Physiol. 277: L204-L217. (Pubitemid 29356769)
16. Plotkowski, M. C., S. de Bentzmann, S. H. Pereira, J. M. Zahm, O. Bajolet-Laudinat, P. Roger, and E. Puchelle. 1999. Pseudomonas aeruginosa internalization by human epithelial respiratory cells depends on cell differentiation, polarity, and junctional complex integrity. Am. J. Respir. Cell Mol. Biol. 20: 880-890. (Pubitemid 129540847)
17. Chi, E., T. Mehl, D. Nunn, and S. Lory. 1991. Interaction of Pseudomonas aeruginosa with A549 pneumocyte cells. Infect. Immun. 59: 822-828.
18. Fleiszig, S. M., T. S. Zaidi, M. J. Preston, M. Grout, D. J. Evans, and G. B. Pier. 1996. Relationship between cytotoxicity and corneal epithelial cell invasion by clinical isolates of Pseudomonas aeruginosa. Infect. Immun. 64: 2288-2294. (Pubitemid 26165690)
19. Cannon, C. L., M. P. Kowalski, K. S. Stopak, and G. B. Pier. 2003. Pseudomonas aeruginosa-induced apoptosis is defective in respiratory epithelial cells expressing mutant cystic fibrosis transmembrane conductance regulator. Am. J. Respir. Cell Mol. Biol. 29: 188-197. (Pubitemid 36936646)
20. Darling, K. E., A. Dewar, and T. J. Evans. 2004. Role of the cystic fibrosis transmembrane conductance regulator in internalization of Pseudomonas aeruginosa by polarized respiratory epithelial cells. Cell. Microbiol. 6: 521-533. (Pubitemid 38618663)
21. Lee, H. S., F. Gu, S. M. Ching, Y. Lam, and K. L. Chua. 2010. CdpA is a Burkholderia pseudomallei cyclic di-GMP phosphodiesterase involved in autoaggregation, flagellum synthesis, motility, biofilm formation, cell invasion, and cytotoxicity. Infect. Immun. 78: 1832-1840.
22. Grassmé, H., S. Kirschnek, J. Riethmueller, A. Riehle, G. von Kürthy, F. Lang, M. Weller, and E. Gulbins. 2000. CD95/CD95 ligand interactions on epithelial cells in host defense to Pseudomonas aeruginosa. Science 290: 527-530
23. Ha, U., and S. Jin. 2001. Growth phase-dependent invasion of Pseudomonas aeruginosa and its survival within HeLa cells. Infect. Immun. 69: 4398-4406. (Pubitemid 32574438)
24. Evans, D. J., D. W. Frank, V. Finck-Barbançon, C. Wu, and S. M. Fleiszig. 1998. Pseudomonas aeruginosa invasion and cytotoxicity are independent events, both of which involve protein tyrosine kinase activity. Infect. Immun. 66: 1453-1459. (Pubitemid 128471504)
25. Massengale, A. R., F. J. Quinn, A. Williams, S. Gallagher, and S. C. Aronoff. 2000. The effect of alginate on the invasion of cystic fibrosis respiratory epithelial cells by clinical isolates of Pseudomonas aeruginosa. Exp. Lung Res. 26: 163-178. (Pubitemid 30241753)
26. Esen, M., H. Grassmé, J. Riethmüller, A. Riehle, K. Fassbender, and E. Gulbins. 2001. Invasion of human epithelial cells by Pseudomonas aeruginosa involves src-like tyrosine kinases p60Src and p59Fyn. Infect. Immun. 69: 281-287. (Pubitemid 32038324)
27. Ding, B., U. Taotofa, T. Orsak, M. Chadwell, and P. B. Savage. 2004. Synthesis and characterization of peptide-cationic steroid antibiotic conjugates. Org. Lett. 6: 3433-3436. (Pubitemid 39406907)
28. Murakami, M., B. Lopez-Garcia, M. Braff, R. A. Dorschner, and R. L. Gallo. 2004. Postsecretory processing generates multiple cathelicidins for enhanced topical antimicrobial defense. J. Immunol. 172: 3070-3077. (Pubitemid 38263696)
29. Isberg, R. R., and S. Falkow. 1985. A single genetic locus encoded by Yersinia pseudotuberculosis permits invasion of cultured animal cells by Escherichia coli K-12. Nature 317: 262-264. (Pubitemid 16246504)
30. Burns, J. L., M. Jonas, E. Y. Chi, D. K. Clark, A. Berger, and A. Griffith. 1996. Invasion of respiratory epithelial cells by Burkholderia (Pseudomonas) cepacia. Infect. Immun. 64: 4054-4059. (Pubitemid 26318122)
31. Byfield, F. J., Q.Wen, K. Leszczynska, A. Kulakowska, Z. Namiot, P. A. Janmey, and R. Bucki. 2011. Cathelicidin LL-37 peptide regulates endothelial cell stiffness and endothelial barrier permeability. Am. J. Physiol. Cell Physiol. 300: C105-C112.
32. Deslouches, B., K. Islam, J. K. Craigo, S. M. Paranjape, R. C. Montelaro, and T. A. Mietzner. 2005. Activity of the de novo engineered antimicrobial peptide WLBU2 against Pseudomonas aeruginosa in human serum and whole blood: implications for systemic applications. Antimicrob. Agents Chemother. 49: 3208-3216. (Pubitemid 41060563)
33. Bucki, R., D. B. Namiot, Z. Namiot, P. B. Savage, and P. A. Janmey. 2008. Salivary mucins inhibit antibacterial activity of the cathelicidin-derived LL-37 peptide but not the cationic steroid CSA-13. J. Antimicrob. Chemother. 62: 329-335. (Pubitemid 351984776)
34. Arce, F. T., J. L. Whitlock, A. A. Birukova, K. G. Birukov, M. F. Arnsdorf, R. Lal, J. G. Garcia, and S. M. Dudek. 2008. Regulation of the micromechanical properties of pulmonary endothelium by S1P and thrombin: role of cortactin. Biophys. J. 95: 886-894.
35. Turner, J., Y. Cho, N. N. Dinh, A. J. Waring, and R. I. Lehrer. 1998. Activities of LL-37, a cathelin-associated antimicrobial peptide of human neutrophils. Antimicrob. Agents Chemother. 42: 2206-2214. (Pubitemid 28420351)
36. Zughaier, S. M., W. M. Shafer, and D. S. Stephens. 2005. Antimicrobial peptides and endotoxin inhibit cytokine and nitric oxide release but amplify respiratory burst response in human and murine macrophages. Cell. Microbiol. 7: 1251-1262. (Pubitemid 41179418)
37. Bucki, R., and P. A. Janmey. 2006. Interaction of the gelsolin-derived antibacterial PBP 10 peptide with lipid bilayers and cell membranes. Antimicrob. Agents Chemother. 50: 2932-2940. (Pubitemid 44403774)
38. Nell, M. J., G. S. Tjabringa, A. R. Wafelman, R. Verrijk, P. S. Hiemstra, J. W. Drijfhout, and J. J. Grote. 2006. Development of novel LL-37 derived antimicrobial peptides with LPS and LTA neutralizing and antimicrobial activities for therapeutic application. Peptides 27: 649-660.
39. Rosenfeld, Y., N. Papo, and Y. Shai. 2006. Endotoxin (lipopolysaccharide) neutralization by innate immunity host-defense peptides. Peptide properties and plausible modes of action. J. Biol. Chem. 281: 1636-1643.
40. Birukova, A. A., F. T. Arce, N. Moldobaeva, S. M. Dudek, J. G. Garcia, R. Lal, and K. G. Birukov. 2009. Endothelial permeability is controlled by spatially defined cytoskeletal mechanics: atomic force microscopy force mapping of pulmonary endothelial monolayer. Nanomedicine 5: 30-41.
41. Lau, G. W., D. J. Hassett, and B. E. Britigan. 2005. Modulation of lung epithelial functions by Pseudomonas aeruginosa. Trends Microbiol. 13: 389-397. (Pubitemid 41073810)
42. Kai-Larsen, Y., and B. Agerberth. 2008. The role of the multifunctional peptide LL-37 in host defense. Front. Biosci. 13: 3760-3767. (Pubitemid 351594656)
43. Nijnik, A., and R. E. Hancock. 2009. The roles of cathelicidin LL-37 in immune defences and novel clinical applications. Curr. Opin. Hematol. 16: 41-47.
44. Barlow, P. G., P. E. Beaumont, C. Cosseau, A. Mackellar, T. S. Wilkinson, R. E. Hancock, C. Haslett, J. R. Govan, A. J. Simpson, and D. J. Davidson. 2010. The human cathelicidin LL-37 preferentially promotes apoptosis of infected airway epithelium. Am. J. Respir. Cell Mol. Biol. 43: 692-702.
45. Tasaka, S., A. Ishizaka, T. Urano, K. Sayama, F. Sakamaki, H. Nakamura, T. Terashima, Y. Waki, K. Soejima, M. Nakamura, et al. 1996. A derivative of cationic antimicrobial protein attenuates lung injury by suppressing cell adhesion. Am. J. Respir. Cell Mol. Biol. 15: 738-744. (Pubitemid 126441446)
46. Fleiszig, S. M., T. S. Zaidi, and G. B. Pier. 1995. Pseudomonas aeruginosa invasion of and multiplication within corneal epithelial cells in vitro. Infect. Immun. 63: 4072-4077.
47. Cowell, B. A., D. J. Evans, and S. M. Fleiszig. 2005. Actin cytoskeleton disruption by ExoY and its effects on Pseudomonas aeruginosa invasion. FEMS Microbiol. Lett. 250: 71-76. (Pubitemid 41138157)
48. Abraham, S. N., M. J. Duncan, G. Li, and D. Zaas. 2005. Bacterial penetration of the mucosal barrier by targeting lipid rafts. J. Investig. Med. 53: 318-321. (Pubitemid 41527772)
49. Yamamoto, N., N. Yamamoto, J. V. Jester, W. M. Petroll, and H. D. Cavanagh. 2006. Prolonged hypoxia induces lipid raft formation and increases Pseudomonas internalization in vivo after contact lens wear and lid closure. Eye Contact Lens 32: 114-120 (Pubitemid 44510035)
50. Kannan, S., A. Audet, J. Knittel, S. Mullegama, G. F. Gao, and M. Wu. 2006. Src kinase Lyn is crucial for Pseudomonas aeruginosa internalization into lung cells. Eur. J. Immunol. 36: 1739-1752. (Pubitemid 44089041)
51. Zaas, D. W., Z. D. Swan, B. J. Brown, G. Li, S. H. Randell, S. Degan, M. E. Sunday, J. R. Wright, and S. N. Abraham. 2009. Counteracting signaling activities in lipid rafts associated with the invasion of lung epithelial cells by Pseudomonas aeruginosa. J. Biol. Chem. 284: 9955-9964.
52. Bucki, R., J. J. Pastore, P. Randhawa, R. Vegners, D. J. Weiner, and P. A. Janmey. 2004. Antibacterial activities of rhodamine B-conjugated gelsolin-derived peptides compared to those of the antimicrobial peptides cathelicidin LL37, magainin II, and melittin. Antimicrob. Agents Chemother. 48: 1526-1533. (Pubitemid 38544355)
53. Sandgren, S., A. Wittrup, F. Cheng, M. Jönsson, E. Eklund, S. Busch, and M. Belting. 2004. The human antimicrobial peptide LL-37 transfers extracellular DNA plasmid to the nuclear compartment of mammalian cells via lipid rafts and proteoglycan-dependent endocytosis. J. Biol. Chem. 279: 17951-17956 (Pubitemid 38568102)
54. Shaykhiev, R., J. Sierigk, C. Herr, G. Krasteva, W. Kummer, and R. Bals. 2010. The antimicrobial peptide cathelicidin enhances activation of lung epithelial cells by LPS. FASEB J. 24: 4756-4766.
55. Huang, H., J. Sylvan, M. Jonas, R. Barresi, P. T. So, K. P. Campbell, and R. T. Lee. 2005. Cell stiffness and receptors: evidence for cytoskeletal subnet-works. Am. J. Physiol. Cell Physiol. 288: C72-C80. (Pubitemid 39658429)
56. Wagh, A. A., E. Roan, K. E. Chapman, L. P. Desai, D. A. Rendon, E. C. Eckstein, and C. M. Waters. 2008. Localized elasticity measured in epithelial cells migrating at a wound edge using atomic force microscopy. Am. J. Physiol. Lung Cell. Mol. Physiol. 295: L54-L60.
57. Heilborn, J. D., M. F. Nilsson, G. Kratz, G. Weber, O. Sørensen, N. Borregaard, and M. Sta° hle-Bäckdahl. 2003. The cathelicidin anti-microbial peptide LL-37 is involved in re-epithelialization of human skin wounds and is lacking in chronic ulcer epithelium. J. Invest. Dermatol. 120: 379-389. (Pubitemid 36298423)