Department of Immunology, Allergy and Infectious Disease, University of New South Wales, St. George Hospital, 2 South St., Kogarah, NSW 2217, Sydney, Australia.
J Autoimmun. 2010 Nov;35(3):232-40. doi: 10.1016/j.jaut.2010.06.013. Epub 2010 Jul 24.
Beta 2 glycoprotein I (β2GPI) is the major auto antigen in the antiphospholipid syndrome but also interacts with fibrinolytic and angiogenic proteins. The aim of this study was to examine the angiogenic potential of β2GPI in vivo in β2GPI deficient mice utilizing angiogenic assays. β2GPI deficient mice show increased microvessel formation in comparison to β2GPI replete controls when injected with growth factor free-matrigel implants. However, microvessel formation in matrigel plugs of β2GPI deficient mice was less than in β2GPI replete mice when basic fibroblast growth factor (bFGF) was included in the matrigel. Hemoglobin content was higher in vascular endothelial growth factor (VEGF) containing-matrigel plugs in the β2GPI deficient mouse demonstrating that the lack of β2GPI led to increased extravasation by VEGF. Melanoma B16F10 tumour growth was enhanced in β2GPI deficient mice. Melanoma microvessel density was increased in β2GPI deficient mice but the proliferation rate of tumour cells (determined by Ki67 immunohistochemistry) was unaffected by the presence or absence of β2GPI. Subcutaneous delivery of native human β2GPI by the ALZET osmotic pump did not affect melanoma tumour growth in β2GPI deficient mice. We conclude that the in vivo unopposed action of β2GPI is anti-angiogenic however this function is modified in the presence of a strong angiogenic stimulus into stabilization of vessel formation. Although the presence of β2GPI attenuates vessel sprouting in certain tumours, no survival benefit is conferred to tumour bearing animals. This does not preclude the potential benefit of modified or fragments of β2GPI in anti-angiogenesis research.
β2 糖蛋白 I（β2GPI）是抗磷脂综合征中的主要自身抗原，但也与纤维蛋白溶解和血管生成蛋白相互作用。本研究旨在通过血管生成测定法，在β2GPI 缺乏的小鼠体内检查β2GPI 的血管生成潜力。与β2GPI 充足的对照相比，当注射不含生长因子的基质胶植入物时，β2GPI 缺乏的小鼠显示出更多的微血管形成。然而，当在基质胶中包含碱性成纤维细胞生长因子（bFGF）时，β2GPI 缺乏的小鼠的基质胶塞中的微血管形成少于β2GPI 充足的小鼠。血管内皮生长因子（VEGF）含量较高的基质胶塞中的血红蛋白含量在β2GPI 缺乏的小鼠中表明，β2GPI 的缺乏导致 VEGF 引起的血管外渗增加。黑色素瘤 B16F10 肿瘤生长在β2GPI 缺乏的小鼠中增强。β2GPI 缺乏的小鼠中黑色素瘤微血管密度增加，但肿瘤细胞的增殖率（通过 Ki67 免疫组织化学测定）不受β2GPI 的存在与否的影响。通过 ALZET 渗透泵皮下递送天然人β2GPI 不会影响β2GPI 缺乏的小鼠中的黑色素瘤肿瘤生长。我们得出结论，β2GPI 在体内的拮抗作用是抗血管生成的，但是在存在强烈的血管生成刺激时，这种作用会被改变为稳定血管形成。尽管β2GPI 的存在会减弱某些肿瘤中的血管发芽，但不会为携带肿瘤的动物带来生存益处。这并不排除β2GPI 的改性或片段在抗血管生成研究中的潜在益处。
