Identification of integrin αMβ2 as an adhesion receptor on peripheral blood monocytes for Cyr61 (CCN1) and connective tissue growth factor (CCN2):: immediate-early gene products expressed in atherosclerotic lesions
Identification of integrin αMβ2 as an adhesion receptor on peripheral blood monocytes for Cyr61 (CCN1) and connective tissue growth factor (CCN2):: immediate-early gene products expressed in atherosclerotic lesions
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DOI：
10.1182/blood.v99.12.4457
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发表时间：
2002-06-15
期刊：
影响因子：
20.3
通讯作者：
Lam, SCT
中科院分区：
文献类型：
--
作者：
Schober, JM;Chen, NY;Lam, SCT
富含半胱氨酸61（Cyr 61，CCN 1）和结缔组织生长因子（CTGF，CCN 2）是在血管壁和愈合的皮肤伤口中发现的生长因子诱导的立即早期基因产物。我们以前报道过内皮细胞、血小板和成纤维细胞与这些细胞外基质相关蛋白的粘附是通过整合素受体介导的。在这项研究中，我们证明Cyr 61和CTGF在载脂蛋白E缺陷小鼠的晚期动脉粥样硬化病变中表达。由于单核细胞粘附和迁移对于动脉粥样硬化、伤口愈合和炎症是重要的，我们研究了THP-1单核细胞和分离的外周血单核细胞与Cyr 61和CTGF的相互作用。THP-1细胞和单核细胞以活化依赖性方式粘附于Cyr 61或CTGF包被的威尔斯孔，该过程主要通过整合素α（M）β（2）介导。此外，在人胚肾293细胞上表达α（M）β（2）导致细胞对Cyr 61的粘附增强。与这些数据一致，GST融合蛋白含有I结构域的整合素α m亚基结合特异性固定Cyr 61或CTGF。我们还研究了细胞表面硫酸乙酰肝素蛋白多糖（HSPGs）作为单核细胞粘附Cyr 61的辅助受体的要求。用肝素或肝素酶I预处理单核细胞导致细胞粘附到Cyr 61的部分抑制。然而，单核细胞，而不是成纤维细胞，能够粘附到Cyr 61突变体缺乏肝素结合活性。总的来说，这些结果表明活化的单核细胞通过整合素α（M）β（2）和细胞表面HSPG粘附于Cyr 61和CTGF。然而，与成纤维细胞粘附于Cyr 61不同，细胞表面HSPG对于该粘附过程不是绝对必需的。(C)2002年，美国血液学会。
Cysteine-rich 61 (Cyr61, CCN1) and connective tissue growth factor (CTGF, CCN2) are growth factor-inducible immediate-early gene products found in blood vessel walls and healing cutaneous wounds. We previously reported that the adhesion of endothelial cells, platelets, and fibroblasts to these extracellular matrix-associated proteins is mediated through integrin receptors. In this study, we demonstrated that both Cyr61 and CTGF are expressed in advanced atherosclerotic lesions of apolipoprotein E-deficient mice. Because monocyte adhesion and transmigration are important for atherosclerosis, wound healing, and inflammation, we examined the interaction of THP-1 monocytic cells and isolated peripheral blood monocytes with Cyr61 and CTGF. THP-1 cells and monocytes adhered to Cyr61- or CTGF-coated wells in an activation-dependent manner and this process was mediated primarily through integrin alpha(M)beta(2). Additionally, expression of alpha(M)beta(2) on human embryonic kidney 293 cells resulted in enhanced cell adhesion to Cyr61. Consistent with these data, a GST-fusion protein containing the I domain of the integrin am subunit bound specifically to immobilized Cyr61 or CTGF. We have also investigated the requirement of cell surface heparan sulfate proteoglycans (HSPGs) as coreceptors for monocyte adhesion to Cyr61. Pretreatment of monocytes with heparin or heparinase I resulted in partial inhibition of cell adhesion to Cyr61. However, monocytes, but not fibroblasts, were capable of adhering to a Cyr61 mutant deficient in heparin binding activity. Collectively, these results show that activated monocytes adhere to Cyr61 and CTGF through integrin alpha(M)beta(2) and cell surface HSPGs. However, unlike fibroblast adhesion to Cyr61, cell surface HSPGs are not absolutely required for this adhesion process. (C) 2002 by The American Society of Hematology.