Baltz M L, Caspi D, Evans D J, Rowe I F, Hind C R, Pepys M B
Clin Exp Immunol. 1986 Dec;66(3):691-700.
Intravenous administration of 125I-labelled isolated mouse serum amyloid P component (SAP) to mice with systemic amyloidosis was followed by specific deposition of the labelled protein in amyloidotic organs. Although only a small proportion of the total injected dose became localized in this way, the amount correlated with the quantity of amyloid present in different organs and was greatest in the spleen. No such localization was detected in the organs of control, untreated mice or animals which had received inflammatory stimuli but did not have amyloidosis. The labelled SAP was found by autoradiography to be present in the same distribution within the tissues as the Congophilic amyloid deposits. These observations establish directly, for the first time, that circulating SAP is the precursor of the amyloid P component (AP) in systemic amyloidosis. They were confirmed by the further finding that intravenous injection into amyloidotic mice of human SAP, either in whole human serum or in isolated pure form, was followed by appearance of the human SAP in the mouse amyloid deposits. In addition to elucidating one aspect of the pathogenesis of amyloid deposition and strengthening the homology of functional behaviour between SAP of different species, the present results suggest a means for selective targeting of diagnostic tracers and/or effector agents to amyloid deposits in vivo.
给患有全身性淀粉样变性的小鼠静脉注射125I标记的分离的小鼠血清淀粉样蛋白P成分(SAP)后,标记蛋白在淀粉样变性器官中特异性沉积。虽然仅一小部分注射的总剂量以这种方式定位,但该量与不同器官中存在的淀粉样蛋白量相关,并且在脾脏中最大。在对照、未治疗的小鼠或接受炎症刺激但没有淀粉样变性的动物的器官中未检测到这种定位。通过放射自显影发现标记的SAP在组织中的分布与嗜刚果红淀粉样沉积物相同。这些观察首次直接证实,循环中的SAP是全身性淀粉样变性中淀粉样蛋白P成分(AP)的前体。进一步的发现证实了这一点,即向淀粉样变性小鼠静脉注射全人血清或分离的纯形式的人SAP后,人SAP出现在小鼠淀粉样沉积物中。除了阐明淀粉样蛋白沉积发病机制的一个方面并加强不同物种SAP之间功能行为的同源性外,目前的结果还提示了一种在体内将诊断示踪剂和/或效应剂选择性靶向淀粉样沉积物的方法。