Imperial College London

DrJamesPease

Faculty of MedicineNational Heart & Lung Institute

Reader in Leukocyte Biology
 
 
 
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Contact

 

+44 (0)20 7594 3162j.pease Website

 
 
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Location

 

109Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Gela:2016:10.1111/all.12771,
author = {Gela, A and Kasetty, G and Morgelin, M and Bergqvist, A and Erjefalt, JS and Pease, JE and Egesten, A},
doi = {10.1111/all.12771},
journal = {Allergy},
pages = {58--67},
title = {Osteopontin binds and modulates functions of eosinophil-recruiting chemokines},
url = {http://dx.doi.org/10.1111/all.12771},
volume = {71},
year = {2016}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - BackgroundAllergic asthma is characterized by eosinophilic inflammation and airway obstruction. There is also an increased risk of pulmonary infection caused by Streptococcus pneumoniae, in particular during severe asthma where high levels of the glycoprotein, osteopontin (OPN), are present in the airways. Eosinophils can be recruited by chemokines activating the receptor CCR3 including eotaxin-1/CCL11, eotaxin-2/CCL24, eotaxin-3/CCL26, RANTES/CCL5, and MEC/CCL28. In addition to inducing chemotaxis, several of these molecules have defensin-like antibacterial properties. This study set out to elucidate the functional consequences of OPN binding to eosinophil-recruiting chemokines.MethodsAntibacterial activities of the chemokines were investigated using viable count assays and electron microscopy. Binding studies were performed by means of surface plasmon resonance. The potential interference of OPN with antibacterial, receptor-activating, and lipopolysaccharide-neutralizing abilities of these chemokines was investigated.ResultsWe found that OPN bound all eosinophil-recruiting chemokines with high affinity except for CCL5. The eosinophil-recruiting chemokines all displayed bactericidal activity against S. pneumoniae, but only CCL26 and CCL28 retained high antibacterial activity in the presence of sodium chloride at physiologic concentrations. Preincubation of the chemokines with OPN strongly inhibited their antibacterial activity against S. pneumoniae but did not affect their ability to activate CCR3. All chemokines investigated showed LPS-neutralizing activity that was impaired by OPN only in the case of CCL24.ConclusionsThe data suggest that OPN may impair host defense activities of the chemokines without affecting their eosinophil-recruiting properties. This could be one mechanism explaining the increased vulnerability to acquire pneumococcal infection in parallel with sustained allergic inflammation in asthma.
AU - Gela,A
AU - Kasetty,G
AU - Morgelin,M
AU - Bergqvist,A
AU - Erjefalt,JS
AU - Pease,JE
AU - Egesten,A
DO - 10.1111/all.12771
EP - 67
PY - 2016///
SN - 0105-4538
SP - 58
TI - Osteopontin binds and modulates functions of eosinophil-recruiting chemokines
T2 - Allergy
UR - http://dx.doi.org/10.1111/all.12771
VL - 71
ER -