Journal article
Inactivation of human beta-defensins 2 and 3 by elastolytic cathepsins
The Journal of immunology (1950), Vol.171(2), pp.931-937
07/15/2003
DOI: 10.4049/jimmunol.171.2.931
PMID: 12847264
Abstract
beta-Defensins are antimicrobial peptides that contribute to the innate immune responses of eukaryotes. At least three defensins, human beta-defensins 1, 2, and 3 (HBD-1, -2, and -3), are produced by epithelial cells lining the respiratory tract and are active toward Gram-positive (HBD-3) and Gram-negative (HBD-1, -2, and -3) bacteria. It has been postulated that the antimicrobial activity of defensins is compromised by changes in airway surface liquid composition in lungs of patients with cystic fibrosis (CF), therefore contributing to the bacterial colonization of the lung by Pseudomonas and other bacteria in CF. In this report we demonstrate that HBD-2 and HBD-3 are susceptible to degradation and inactivation by the cysteine proteases cathepsins B, L, and S. In addition, we show that all three cathepsins are present and active in CF bronchoalveolar lavage. Incubation of HBD-2 and -3 with CF bronchoalveolar lavage leads to their degradation, which can be completely (HBD-2) or partially (HBD-3) inhibited by a cathepsin inhibitor. These results suggest that beta-defensins are susceptible to degradation and inactivation by host proteases, which may be important in the regulation of beta-defensin activity. In chronic lung diseases associated with infection, overexpression of cathepsins may lead to increased degradation of HBD-2 and -3, thereby favoring bacterial infection and colonization.
Details
- Title: Subtitle
- Inactivation of human beta-defensins 2 and 3 by elastolytic cathepsins
- Creators
- Clifford C Taggart - Pulmonary Research Division, Department of Medicine, Royal College of Surgeons in Ireland, Education and Research Center, Beaumont Hospital, Dublin, Ireland. ctaggart@rcsi.i.eCatherine M GreeneStephen G SmithRodney L LevinePaul B McCray JrShane O'NeillNoel G McElvaney
- Resource Type
- Journal article
- Publication Details
- The Journal of immunology (1950), Vol.171(2), pp.931-937
- DOI
- 10.4049/jimmunol.171.2.931
- PMID
- 12847264
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Language
- English
- Date published
- 07/15/2003
- Academic Unit
- Microbiology and Immunology; Pulmonary Medicine; Stead Family Department of Pediatrics; Internal Medicine
- Record Identifier
- 9984093329002771
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