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

<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&gt