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Eotaxin-3 (CCL26) exerts innate host defense activities that are modulated by mast cell proteases

Gela, Anele LU ; Kasetty, Gopinath LU ; Jovic, Sandra LU ; Ekoff, M.; Nilsson, G.; Mörgelin, Matthias LU ; Kjellstrom, S.; Pease, J. E.; Schmidtchen, A. and Egesten, Arne LU (2015) In Allergy 70(2). p.161-170
Abstract
BackgroundDuring bacterial infections of the airways, a Th1-profiled inflammation promotes the production of several host defense proteins and peptides with antibacterial activities including -defensins, ELR-negative CXC chemokines, and the cathelicidin LL-37. These are downregulated by Th2 cytokines of the allergic response. Instead, the eosinophil-recruiting chemokines eotaxin-1/CCL11, eotaxin-2/CCL24, and eotaxin-3/CCL26 are expressed. This study set out to investigate whether these chemokines could serve as innate host defense molecules during allergic inflammation. MethodsAntibacterial activities of the eotaxins were investigated using viable count assays, electron microscopy, and methods assessing bacterial permeabilization.... (More)
BackgroundDuring bacterial infections of the airways, a Th1-profiled inflammation promotes the production of several host defense proteins and peptides with antibacterial activities including -defensins, ELR-negative CXC chemokines, and the cathelicidin LL-37. These are downregulated by Th2 cytokines of the allergic response. Instead, the eosinophil-recruiting chemokines eotaxin-1/CCL11, eotaxin-2/CCL24, and eotaxin-3/CCL26 are expressed. This study set out to investigate whether these chemokines could serve as innate host defense molecules during allergic inflammation. MethodsAntibacterial activities of the eotaxins were investigated using viable count assays, electron microscopy, and methods assessing bacterial permeabilization. Fragments generated by mast cell proteases were characterized, and their potential antibacterial, receptor-activating, and lipopolysaccharide-neutralizing activities were investigated. ResultsCCL11, CCL24, and CCL26 all showed potent bactericidal activity, mediated through membrane disruption, against the airway pathogens Streptococcus pneumoniae, Staphylococcus aureus, Nontypeable Haemophilus influenzae, and Pseudomonas aeruginosa. CCL26 retained bactericidal activity in the presence of salt at physiologic concentrations, and the region holding the highest bactericidal activity was the cationic and amphipathic COOH-terminus. Proteolysis of CCL26 by chymase and tryptase, respectively, released distinct fragments of the COOH- and NH2-terminal regions. The COOH-terminal fragment retained antibacterial activity while the NH2-terminal had potent LPS-neutralizing properties in the order of CCL26 full-length protein. An identical fragment to NH2-terminal fragment generated by tryptase was obtained after incubation with supernatants from activated mast cells. None of the fragments activated the CCR3-receptor. ConclusionsTaken together, the findings show that the eotaxins can contribute to host defense against common airway pathogens and that their activities are modulated by mast cell proteases. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
allergy, bacterial infection, eotaxins, host defense
in
Allergy
volume
70
issue
2
pages
161 - 170
publisher
Wiley-Blackwell
external identifiers
  • wos:000347960300004
  • scopus:84920854807
ISSN
1398-9995
DOI
10.1111/all.12542
language
English
LU publication?
yes
id
1708508b-7b41-4e79-95cd-381041ac736f (old id 5053305)
date added to LUP
2015-03-02 07:14:38
date last changed
2017-03-26 03:46:02
@article{1708508b-7b41-4e79-95cd-381041ac736f,
  abstract     = {BackgroundDuring bacterial infections of the airways, a Th1-profiled inflammation promotes the production of several host defense proteins and peptides with antibacterial activities including -defensins, ELR-negative CXC chemokines, and the cathelicidin LL-37. These are downregulated by Th2 cytokines of the allergic response. Instead, the eosinophil-recruiting chemokines eotaxin-1/CCL11, eotaxin-2/CCL24, and eotaxin-3/CCL26 are expressed. This study set out to investigate whether these chemokines could serve as innate host defense molecules during allergic inflammation. MethodsAntibacterial activities of the eotaxins were investigated using viable count assays, electron microscopy, and methods assessing bacterial permeabilization. Fragments generated by mast cell proteases were characterized, and their potential antibacterial, receptor-activating, and lipopolysaccharide-neutralizing activities were investigated. ResultsCCL11, CCL24, and CCL26 all showed potent bactericidal activity, mediated through membrane disruption, against the airway pathogens Streptococcus pneumoniae, Staphylococcus aureus, Nontypeable Haemophilus influenzae, and Pseudomonas aeruginosa. CCL26 retained bactericidal activity in the presence of salt at physiologic concentrations, and the region holding the highest bactericidal activity was the cationic and amphipathic COOH-terminus. Proteolysis of CCL26 by chymase and tryptase, respectively, released distinct fragments of the COOH- and NH2-terminal regions. The COOH-terminal fragment retained antibacterial activity while the NH2-terminal had potent LPS-neutralizing properties in the order of CCL26 full-length protein. An identical fragment to NH2-terminal fragment generated by tryptase was obtained after incubation with supernatants from activated mast cells. None of the fragments activated the CCR3-receptor. ConclusionsTaken together, the findings show that the eotaxins can contribute to host defense against common airway pathogens and that their activities are modulated by mast cell proteases.},
  author       = {Gela, Anele and Kasetty, Gopinath and Jovic, Sandra and Ekoff, M. and Nilsson, G. and Mörgelin, Matthias and Kjellstrom, S. and Pease, J. E. and Schmidtchen, A. and Egesten, Arne},
  issn         = {1398-9995},
  keyword      = {allergy,bacterial infection,eotaxins,host defense},
  language     = {eng},
  number       = {2},
  pages        = {161--170},
  publisher    = {Wiley-Blackwell},
  series       = {Allergy},
  title        = {Eotaxin-3 (CCL26) exerts innate host defense activities that are modulated by mast cell proteases},
  url          = {http://dx.doi.org/10.1111/all.12542},
  volume       = {70},
  year         = {2015},
}