Differential regulation of monocyte cytokine release by αv and β2 integrins that bind CD23

Edkins, A.L., Borland, G., Acharya, M., Cogdell, R.J. , Ozanne, B.W. and Cushley, W. (2012) Differential regulation of monocyte cytokine release by αv and β2 integrins that bind CD23. Immunology, 136(2), pp. 241-251. (doi:10.1111/j.1365-2567.2012.03576.x)

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Abstract

<p>The human soluble CD23 (sCD23) protein displays highly pleiotropic cytokine-like activity. Monocytic cells express the sCD23-binding integrins αvβ3, αvβ5, αMβ2 and αXβ2, but it is unclear which of these four integrins most acutely regulates sCD23-driven cytokine release.</p> <p>The hypothesis that ligation of different sCD23-binding integrins promoted release of distinct subsets of cytokines was tested. Lipopolysaccharide (LPS) and sCD23 promoted release of distinct groups of cytokines from the THP-1 model cell line. The sCD23-driven cytokine release signature was characterised by elevated amounts of RANTES (CCL5) and a striking increase in IL-8 (CXCL8) secretion, but little release of MIP-1β (CCL4.) Antibodies to αvβ3 or αXβ2 both promoted IL-8 release, consistent with the sCD23-driven pattern, but both also evoked strong MIP-1β secretion; simultaneous ligation of these two integrins further increased cytokine secretion but did not alter the pattern of cytokine output. In both model cell lines and primary tissue, integrin-mediated cytokine release was more pronounced in immature monocyte cells than in mature cells.</p> <p>The capacity of anti-integrin MAbs to elicit a cytokine release response is epitope-dependent and also reflects the differentiation state of the cell. Although a pattern of cytokine release identical to that provoked by sCD23 could not be elicited with any individual anti-integrin MAb, αXβ2 and αvβ3 appear to regulate IL-8 release, a hallmark feature of sCD23-driven cytokine secretion, more acutely than αMβ2 or αvβ5.</p>

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Cushley, Professor William and Borland, Dr Gillian and Cogdell, Professor Richard and Ozanne, Professor Bradford
Authors: Edkins, A.L., Borland, G., Acharya, M., Cogdell, R.J., Ozanne, B.W., and Cushley, W.
College/School:College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
College of Medical Veterinary and Life Sciences > School of Life Sciences
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Immunology
ISSN:0019-2805

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