Rix D A, Douglas M S, Talbot D, Dark J H, Kirby J A
Transplant Immunology Unit, Department of Surgery, The Medical School, University of Newcastle, Newcastle upon Tyne, UK.
Clin Exp Immunol. 1996 Apr;104(1):60-5. doi: 10.1046/j.1365-2249.1996.d01-641.x.
Heparan sulphate is a common glycosaminoglycan component of proteoglycans present on the luminal surface of vascular endothelium. It has been proposed that an important function of these molecules is the sequestration of a range of proinflammatory and proadhesive cytokines. Such cytokines play a vital role during lymphocyte recruitment from the blood at sites of inflammation. In this study it is shown that the effects of interferon-gamma (IFN-gamma), but not of tumour necrosis factor-alpha (TNF-alpha), are inhibited by treatment with soluble heparin. Specifically, heparin was shown to inhibit the induction of class II MHC antigens and the up-regulation of intercellular adhesion molecule-1 (ICAM-1) produced by treatment of cultured human endothelial cells with IFN-gamma. Furthermore, it was shown that heparin blocked the enhanced adhesion of T lymphocytes to IFN-gamma-treated endothelial cells. Investigation of the inhibitory effects of other GAG molecules demonstrated a requirement for heparin-like structural domains as chondroitin sulphate was unable to inhibit the function of IFN-gamma. These results may explain reported immunosuppressive properties of heparin, and are consistent with the model that heparin may compete with cell surface GAGs to bind IFN-gamma, thereby reducing effective biological activity.
硫酸乙酰肝素是存在于血管内皮细胞腔表面蛋白聚糖中的一种常见糖胺聚糖成分。有人提出，这些分子的一个重要功能是隔离一系列促炎和促黏附细胞因子。此类细胞因子在炎症部位淋巴细胞从血液中募集的过程中起着至关重要的作用。本研究表明，可溶性肝素处理可抑制干扰素-γ（IFN-γ）的作用，但不抑制肿瘤坏死因子-α（TNF-α）的作用。具体而言，肝素被证明可抑制用IFN-γ处理培养的人内皮细胞所诱导的II类MHC抗原以及细胞间黏附分子-1（ICAM-1）的上调。此外，还表明肝素可阻断T淋巴细胞与IFN-γ处理的内皮细胞增强的黏附。对其他糖胺聚糖分子抑制作用的研究表明，由于硫酸软骨素无法抑制IFN-γ的功能，因此需要类似肝素的结构域。这些结果可能解释了报道的肝素免疫抑制特性，并且与肝素可能与细胞表面糖胺聚糖竞争结合IFN-γ从而降低有效生物活性的模型一致。
