Vascular endothelial growth factor. A cytokine modulating endothelial function in rheumatoid arthritis.
Vascular endothelial growth factor. A cytokine modulating endothelial function in rheumatoid arthritis.
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DOI：
10.4049/jimmunol.152.8.4149
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发表时间：
1994-04
影响因子：
4.4
通讯作者：
A. Koch;A. Koch;L. Harlow;G. K. Haines;E. Amento;E. Unemori;Wei Lee Wong;R. Pope;N. Ferrara
中科院分区：
文献类型：
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作者：
A. Koch;A. Koch;L. Harlow;G. K. Haines;E. Amento;E. Unemori;Wei Lee Wong;R. Pope;N. Ferrara
血管生成在炎性滑膜组织的增殖中是重要的。血管内皮生长因子（VEGF）是一种内皮细胞有丝分裂原，在体内也是血管生成的。我们研究了VEGF在介导类风湿关节炎（RA）中内皮细胞的趋化性和增殖的潜在作用，使用55例关节炎患者的滑膜组织和滑液样本。RA滑液中ELISA法测得的VEGF（386 +/- 122 ng/ml）（SE）高于骨关节炎（OA）滑液（< 0.8 ng/ml）（p < 0.05）或其他关节炎患者的滑液（6.6 +/- 2 ng/ml）。除了已知的促有丝分裂特性外，我们发现人rVEGF在浓度高于0.02 nM时对HUVECs具有趋化性。RA滑液与中和抗VEGF孵育导致HUVEC趋化性抑制23 - 66%（平均53 ± 4%）。从四个RA滑膜组织外植体的条件培养基是促有丝分裂的牛肾上腺毛细血管内皮细胞。抗VEGF中和了19 - 42%（平均28 +/- 4%）的促有丝分裂活性。为了确定滑膜组织中VEGF的细胞来源，我们采用免疫组化。正常滑膜组织中VEGF阳性细胞较少（< 1%+）。相反，RA和OA滑膜组织显示VEGF+衬里细胞（分别为8%和13%）。在RA和OA中，少数滑膜组织巨噬细胞为VEGF+（分别为5%和2%）。这些结果阐明了一个新描述的功能，VEGF作为一种有效的趋化因子的内皮细胞，以及在RA相关的内皮细胞迁移和增殖的VEGF的作用。
Angiogenesis is important in the proliferation of inflammatory synovial tissue. Vascular endothelial growth factor (VEGF) is an endothelial cell mitogen that is also angiogenic in vivo. We examined the potential role of VEGF in mediating chemotaxis and proliferation of endothelial cells in rheumatoid arthritis (RA) using samples of synovial tissue and synovial fluid from 55 arthritic patients. Synovial fluid VEGF by ELISA was higher in RA synovial fluids (386 +/- 122 ng/ml) (SE) compared with osteoarthritis (OA) synovial fluids (< 0.8 ng/ml) (p < 0.05) or synovial fluids from patients with other arthritides (6.6 +/- 2 ng/ml). In addition to its known mitogenic properties, we found that human rVEGF was chemotactic for HUVECs at concentrations above 0.02 nM. Incubation of RA synovial fluids with neutralizing anti-VEGF resulted in 23 to 66% (mean 53 +/- 4%) inhibition of HUVEC chemotaxis. Conditioned medium from four of five RA synovial tissue explants was mitogenic for bovine adrenal capillary endothelial cells. Anti-VEGF neutralized from 19 to 42% (mean 28 +/- 4%) of this mitogenic activity. To determine the cellular source of VEGF in synovial tissue, we employed immunohistochemistry. VEGF+ cells were rarely (< 1%+) found in normal synovial tissues. In contrast, RA and OA synovial tissues exhibited VEGF+ lining cells (8% and 13%, respectively). A few synovial tissue macrophages were VEGF+ in both RA and OA (5% and 2%, respectively). These results elucidate a newly described function for VEGF as a potent chemotaxin for endothelial cells as well as a role for VEGF in RA-associated endothelial migration and proliferation.