College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
Immunology. 2012 Jun;136(2):241-51. doi: 10.1111/j.1365-2567.2012.03576.x.
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).
人可溶性 CD23（sCD23）蛋白具有高度多效性细胞因子样活性。单核细胞表达 sCD23 结合整合素 αVβ(3)、αVβ(5)、αMβ(2)和 αXβ(2)，但尚不清楚这四种整合素中哪一种最能调节 sCD23 驱动的细胞因子释放。测试了不同 sCD23 结合整合素的配体是否促进了不同细胞因子亚群释放的假设。脂多糖 (LPS) 和 sCD23 从 THP-1 模型细胞系中促进了不同细胞因子组的释放。sCD23 驱动的细胞因子释放特征是 RANTES（CCL5）的含量升高，白细胞介素-8（IL-8；CXCL8）的分泌显著增加，但巨噬细胞炎症蛋白 1β（MIP-1β；CCL4）的释放很少。抗 αVβ(3)或 αXβ(2)抗体均促进 IL-8 释放，与 sCD23 驱动的模式一致，但两者也引起强烈的 MIP-1β 分泌；同时结合这两种整合素进一步增加细胞因子分泌，但不改变细胞因子输出模式。在两种模型细胞系和原代组织中，整合素介导的细胞因子释放在前体单核细胞中比在成熟细胞中更为明显。抗整合素单克隆抗体引起细胞因子释放反应的能力依赖于表位，并且还反映了细胞的分化状态。虽然不能用任何单个抗整合素单克隆抗体引发与 sCD23 引发的细胞因子释放反应完全相同的模式，但 αXβ(2)和 αVβ(3)似乎比 αMβ(2)或 αVβ(5)更能调节 IL-8 的释放，这是 sCD23 驱动的细胞因子分泌的一个显著特征。
