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Contribution of eotaxin-1 to eosinophil chemotactic activity of moderate and severe asthmatic sputum

Contribution of eotaxin-1 to eosinophil chemotactic activity of moderate and severe asthmatic sputum
Contribution of eotaxin-1 to eosinophil chemotactic activity of moderate and severe asthmatic sputum
The CC chemokine eotaxin-1 (CCL11) is chemotactic for eosinophils, basophils, and type 2 helper T cells and may play a role in allergic inflammation. We investigated its contribution as an eosinophil chemoattractant in asthmatic airway secretions (sampled as induced sputum), which possess chemotactic activity for eosinophils and T cells. Sputum samples collected from healthy subjects and subjects with mild, stable-moderate, unstable-moderate, and severe asthma were processed with phosphate-buffered saline and assayed for eotaxin by ELISA and for eosinophil chemotactic activity by fluorescence-based chemotaxis assay. The contribution of eotaxin to chemotactic activity was studied by using a high-affinity neutralizing human anti-eotaxin antibody, CAT-213. Sputum eotaxin concentration was significantly raised in moderate and severe asthma (p < 0.05 versus healthy control subjects) but not in mild asthma. Chemotactic activity was significantly increased in all asthmatic groups relative to healthy subjects (p < 0.05) and was significantly inhibited by CAT-213 (100 nM) in subjects with moderate and severe asthma, with median inhibition of 52% (p < 0.05), 78% (p < 0.0001), and 86% (p < 0.0001), respectively, in samples representing stable-moderate, unstable-moderate, and severe asthma. Eotaxin contributed to the eosinophil chemotactic activity of sputum from subjects with more severe forms of asthma but not mild asthma, suggesting that its contribution is more important in more severe disease. This activity is inhibited significantly by CAT-213.
antibodies, asthma, chemokines, chemotaxis
1073-449X
1110-1117
Dent, Gordon
73559f2a-168a-4f3d-b478-f3838e77132f
Hadjicharalambous, Chrystalleni
4659f794-57da-4a3b-9317-1011eab65f65
Yoshikawa, Takahiro
e13f728a-64a7-420d-be6c-5ae6a498bfb1
Handy, Rachel L.C.
98e09f16-af44-4f5a-bfff-9b6beb4ab9a9
Powell, John
0616c5bf-0ce6-48ef-9b89-45a72529beb1
Anderson, Ian K.
d9ca65db-fce4-41cf-9539-3d6552a76783
Louis, Renaud
9d9c7917-f095-4647-abdb-a9725f586170
Davies, Donna E.
7de8fdc7-3640-4e3a-aa91-d0e03f990c38
Djukanovic, Ratko
d9a45ee7-6a80-4d84-a0ed-10962660a98d
Dent, Gordon
73559f2a-168a-4f3d-b478-f3838e77132f
Hadjicharalambous, Chrystalleni
4659f794-57da-4a3b-9317-1011eab65f65
Yoshikawa, Takahiro
e13f728a-64a7-420d-be6c-5ae6a498bfb1
Handy, Rachel L.C.
98e09f16-af44-4f5a-bfff-9b6beb4ab9a9
Powell, John
0616c5bf-0ce6-48ef-9b89-45a72529beb1
Anderson, Ian K.
d9ca65db-fce4-41cf-9539-3d6552a76783
Louis, Renaud
9d9c7917-f095-4647-abdb-a9725f586170
Davies, Donna E.
7de8fdc7-3640-4e3a-aa91-d0e03f990c38
Djukanovic, Ratko
d9a45ee7-6a80-4d84-a0ed-10962660a98d

Dent, Gordon, Hadjicharalambous, Chrystalleni, Yoshikawa, Takahiro, Handy, Rachel L.C., Powell, John, Anderson, Ian K., Louis, Renaud, Davies, Donna E. and Djukanovic, Ratko (2004) Contribution of eotaxin-1 to eosinophil chemotactic activity of moderate and severe asthmatic sputum. American Journal of Respiratory and Critical Care Medicine, 169 (10), 1110-1117. (doi:10.1164/rccm.200306-855OC).

Record type: Article

Abstract

The CC chemokine eotaxin-1 (CCL11) is chemotactic for eosinophils, basophils, and type 2 helper T cells and may play a role in allergic inflammation. We investigated its contribution as an eosinophil chemoattractant in asthmatic airway secretions (sampled as induced sputum), which possess chemotactic activity for eosinophils and T cells. Sputum samples collected from healthy subjects and subjects with mild, stable-moderate, unstable-moderate, and severe asthma were processed with phosphate-buffered saline and assayed for eotaxin by ELISA and for eosinophil chemotactic activity by fluorescence-based chemotaxis assay. The contribution of eotaxin to chemotactic activity was studied by using a high-affinity neutralizing human anti-eotaxin antibody, CAT-213. Sputum eotaxin concentration was significantly raised in moderate and severe asthma (p < 0.05 versus healthy control subjects) but not in mild asthma. Chemotactic activity was significantly increased in all asthmatic groups relative to healthy subjects (p < 0.05) and was significantly inhibited by CAT-213 (100 nM) in subjects with moderate and severe asthma, with median inhibition of 52% (p < 0.05), 78% (p < 0.0001), and 86% (p < 0.0001), respectively, in samples representing stable-moderate, unstable-moderate, and severe asthma. Eotaxin contributed to the eosinophil chemotactic activity of sputum from subjects with more severe forms of asthma but not mild asthma, suggesting that its contribution is more important in more severe disease. This activity is inhibited significantly by CAT-213.

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Published date: 2004
Keywords: antibodies, asthma, chemokines, chemotaxis

Identifiers

Local EPrints ID: 27023
URI: http://eprints.soton.ac.uk/id/eprint/27023
ISSN: 1073-449X
PURE UUID: bc674c1e-73b1-4ffd-9acc-e353e95da9c5
ORCID for Donna E. Davies: ORCID iD orcid.org/0000-0002-5117-2991
ORCID for Ratko Djukanovic: ORCID iD orcid.org/0000-0001-6039-5612

Catalogue record

Date deposited: 24 Apr 2006
Last modified: 03 Dec 2019 02:07

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Contributors

Author: Gordon Dent
Author: Chrystalleni Hadjicharalambous
Author: Takahiro Yoshikawa
Author: Rachel L.C. Handy
Author: John Powell
Author: Ian K. Anderson
Author: Renaud Louis
Author: Donna E. Davies ORCID iD

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