Perera Binura, Wu Yuao, Pickett Jessica R, Panagides Nadya, Barretto Francisca M, Fercher Christian, Sester David P, Jones Martina L, Ta Hang T, Zacchi Lucia F
ARC Training Centre for Biopharmaceutical Innovation, Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St. Lucia, QLD 4072, Australia.
Queensland Micro- and Nanotechnology Centre, Griffith University, Nathan, QLD 4111, Australia.
Int J Mol Sci. 2024 Dec 20;25(24):13650. doi: 10.3390/ijms252413650.
The vascular cell adhesion molecule-1 (VCAM-1) plays an important role in inflammation, where it facilitates the recruitment of leukocytes to the inflamed area via leukocytes' VLA-4 and endothelial cells' VCAM-1 interaction. VCAM-1 expression is also upregulated in certain cancers. VCAM-1 has seven Ig-like domains, with domains 1 and 4 shown to be critical for VLA-4 binding. However, the specific functions of individual VCAM-1 Ig-like domains remain poorly understood. In this study, we identified single-chain variable fragment (scFv) antibodies targeting domains 2, 3, and 5 of VCAM-1, and investigated the ability of these antibodies to block VCAM-1-mediated cell adhesion to macrophages. We show that scFv antibodies against Ig-like domains 2 and 3 interfere with the ability of macrophages to bind endothelial cells, suggesting that these domains also play a role in facilitating this interaction. These results emphasize the need to more carefully study the role of each domain on VCAM-1 function and highlight the potential of targeting these VCAM-1 domains for more tailored therapeutic interventions in inflammatory diseases and cancer.
血管细胞黏附分子-1（VCAM-1）在炎症中起重要作用，它通过白细胞的VLA-4与内皮细胞的VCAM-1相互作用，促进白细胞募集到炎症区域。VCAM-1的表达在某些癌症中也会上调。VCAM-1有七个免疫球蛋白样结构域，已证明结构域1和4对VLA-4结合至关重要。然而，单个VCAM-1免疫球蛋白样结构域的具体功能仍知之甚少。在本研究中，我们鉴定了靶向VCAM-1结构域2、3和5的单链可变片段（scFv）抗体，并研究了这些抗体阻断VCAM-1介导的细胞与巨噬细胞黏附的能力。我们发现，针对免疫球蛋白样结构域2和3的scFv抗体干扰了巨噬细胞与内皮细胞结合的能力，这表明这些结构域在促进这种相互作用中也发挥作用。这些结果强调需要更仔细地研究每个结构域在VCAM-1功能中的作用，并突出了靶向这些VCAM-1结构域在炎症性疾病和癌症中进行更具针对性治疗干预的潜力。
