Michel J B, Guettier C, Reade R, Sayah S, Corvol P, Ménard J
Institut National de la Santé et de la Recherche Médicale, Paris, France.
Am Heart J. 1989 Mar;117(3):756-67. doi: 10.1016/0002-8703(89)90767-9.
Several immunologic approaches to blockade of the renin-angiotensin system (RAS) have been reported, involving most of the proteins and peptides of the biochemical cascade: renin, substrate, angiotensins, and converting enzyme. None as yet has involved blockade of angiotensin II receptors. Earlier and more recent studies used passive transfer of heterologous antibodies or active immunization against RAS proteins and peptides. Passive transfers have been performed with both polyclonal antibodies and now with specific monoclonal immunoglobulins. The latter are better defined in affinity, quantity, and capacity to bind and thus inhibit the biologic activity of the antigen. Active immunization produced long-term blockade of part or all of the biologic activity of the system. The immunopathologic consequences of the use of antibodies raised against a self-antigen could be of interest in defining the predominant site of storage and secretion of the relevant protein and hence the respective roles of different tissues in the production of specific proteins in, for example, the vascular pulmonary bed for converting enzyme and renal arterial tree for renin. In all cases immunologic methods offer in vivo experimental models of short- or long-term RAS blockade that could be compared with pharmacologic methods, such as converting-enzyme inhibition, angiotensin II antagonists, and renin inhibitors.
据报道,有几种免疫方法可用于阻断肾素-血管紧张素系统(RAS),涉及生化级联反应中的大多数蛋白质和肽:肾素、底物、血管紧张素和转化酶。目前尚无涉及阻断血管紧张素II受体的方法。早期和近期的研究采用了异源抗体的被动转移或针对RAS蛋白质和肽的主动免疫。被动转移既使用了多克隆抗体,现在也使用了特异性单克隆免疫球蛋白。后者在亲和力、数量以及结合并因此抑制抗原生物活性的能力方面定义更明确。主动免疫可长期阻断该系统部分或全部的生物活性。针对自身抗原产生的抗体的免疫病理后果,可能有助于确定相关蛋白质储存和分泌的主要部位,从而明确不同组织在特定蛋白质产生过程中的各自作用,例如在血管肺床中转化酶的产生以及在肾动脉树中肾素的产生。在所有情况下,免疫方法都提供了短期或长期RAS阻断的体内实验模型,可与药理学方法进行比较,如转化酶抑制、血管紧张素II拮抗剂和肾素抑制剂。