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Osteopontin binds and modulates functions of eosinophil‐recruiting chemokines
Author(s) -
Gela A.,
Kasetty G.,
Mörgelin M.,
Bergqvist A.,
Erjefält J. S.,
Pease J. E.,
Egesten A.
Publication year - 2016
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/all.12771
Subject(s) - eotaxin , chemokine , ccl11 , ccr3 , eosinophil peroxidase , ccl5 , eosinophil , immunology , allergic inflammation , chemotaxis , chemistry , osteopontin , ccl7 , chemokine receptor , biology , inflammation , receptor , immune system , asthma , t cell , biochemistry , il 2 receptor
Background Allergic 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 CCR 3 including eotaxin‐1/ CCL 11, eotaxin‐2/ CCL 24, eotaxin‐3/ CCL 26, RANTES / CCL 5, and MEC / CCL 28. 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. Methods Antibacterial 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. Results We found that OPN bound all eosinophil‐recruiting chemokines with high affinity except for CCL 5. The eosinophil‐recruiting chemokines all displayed bactericidal activity against S. pneumoniae , but only CCL 26 and CCL 28 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 CCR 3. All chemokines investigated showed LPS ‐neutralizing activity that was impaired by OPN only in the case of CCL 24. Conclusions The 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.