title: Differential regulation of monocyte cytokine release by αV and β(2)  integrins that bind CD23.
abstract: The human soluble CD23 (sCD23) protein displays highly pleiotropic cytokine-like activity. Monocytic cells express the sCD23-binding integrins αVβ(3), αVβ(5), αMβ(2) and αXβ(2), 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 αVβ(3) or αXβ(2) 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, αXβ(2) and αVβ(3) appear to regulate IL-8 release, a hallmark feature of sCD23-driven cytokine secretion, more acutely than αMβ(2) or αVβ(5).
authors.affiliation: College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
authors.forename: Adrienne L
authors.initials: AL
authors.lastname: Edkins
authors.forename: Gillian
authors.initials: G
authors.lastname: Borland
authors.forename: Mridu
authors.initials: M
authors.lastname: Acharya
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Cogdell
authors.forename: Bradford W
authors.initials: BW
authors.lastname: Ozanne
authors.forename: William
authors.initials: W
authors.lastname: Cushley
mesh_terms: D057134:Antibodies, Neutralizing / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism*; D006801:Humans; D039001:Integrin alpha Chains / Q000037:antagonists & inhibitors / Q000737:chemistry*; D039641:Integrin beta Chains / Q000737:chemistry* / Q000187:drug effects; D008070:Lipopolysaccharides / Q000737:chemistry / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D017455:Receptors, IgE / Q000037:antagonists & inhibitors / Q000737:chemistry*
chemical_list: D057134:Antibodies, Neutralizing; D016207:Cytokines; D039001:Integrin alpha Chains; D039641:Integrin beta Chains; D008070:Lipopolysaccharides; D017455:Receptors, IgE