Soluble semaphorin 4D (SEMA4D) is a 120 kDa transmembrane protein, which belongs to the semaphorin family of axon guidance molecules that act primarily axonal repellents. SEMA4D elicits its migration-promoting and immunomodulatory effects through activation of PLXNB1 and CD72, respectively. In this study, SEMA4D combined with heparin were adsorbed onto cationic surfaces. The biocompatibility evaluation results indicated that the SEMA4D-heparin-modified surfaces displayed less platelet adhesion and activation, prolonged activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT) and reduced fibrinogen gamma chain (FGG) exposure and fibrinogen adhesion. Additionally, endothelial cells (ECs) showed improved adhesion density and proliferation activity on the SEMA4D-heparin-modified surfaces. Chemotactic and haptotaxis assays indicated a highly guided migration for ECs on the modified surfaces. The immunological tests revealed that the SEMA4D-heparin complexes had a positive immunomodulatory effect on macrophages and promoted macrophages polarization into M2 phenotypes. Overall, the results suggested that the SEMA4D-heparin complexes can be a potential therapeutic agent to promote tissue healing and accelerate in situ endothelialization with minimal side effects and positive immunomodulatory effect.

中文翻译：

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固定在钛表面上的SEMA4D-肝素复合物具有抗凝，促进细胞迁移和免疫调节作用。

可溶性信号量蛋白4D（SEMA4D）是一种120 kDa的跨膜蛋白，属于主要作用于轴突驱避剂的轴突引导分子信号蛋白家族。SEMA4D分别通过激活PLXNB1和CD72来引发其迁移促进和免疫调节作用。在这项研究中，SEMA4D与肝素结合被吸附到阳离子表面上。生物相容性评估结果表明，SEMA4D-肝素修饰的表面显示较少的血小板粘附和激活，延长了部分凝血活酶时间（APTT），凝血酶原时间（PT）和凝血酶时间（TT）的活化，并降低了纤维蛋白原γ链的暴露量和纤维蛋白原粘附。此外，内皮细胞（ECs）在SEMA4D-肝素修饰的表面上显示出改善的黏附密度和增殖活性。趋化和触觉分析表明ECs在改性表面上有高度引导的迁移。免疫学测试表明，SEMA4D-肝素复合物对巨噬细胞具有积极的免疫调节作用，并促进巨噬细胞极化为M2型。总体而言，结果表明，SEMA4D-肝素复合物可以作为潜在的治疗剂，以最小的副作用和积极的免疫调节作用，促进组织愈合并加速原位内皮化。