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

• Published in: Immunology 2012-06, Vol.136 (2), p.241-251
• Main Authors: Edkins, Adrienne L., Borland, Gillian, Acharya, Mridu, Cogdell, Richard J., Ozanne, Bradford W., Cushley, William
• Format: Article
• Language: English
• Subjects: CD23; cytokine release; integrins; Original
• ISSN: 0019-2805; 1365-2567
• DOI: 10.1111/j.1365-2567.2012.03576.x

Summary 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. 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 characterized by elevated amounts of RANTES (CCL5) and a striking increase in interleukin‐8 (IL‐8; CXCL8) secretion, but little release of macrophage inflammatory protein 1β (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. The capacity of anti‐integrin monoclonal antibodies 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 monoclonal antibody, αXβ2 and αVβ3 appear to regulate IL‐8 release, a hallmark feature of sCD23‐driven cytokine secretion, more acutely than αMβ2 or αVβ5.