Roccatello D, Isidoro C, Mazzucco G, Mesiti A, Quattrocchio G, Amore A, Molino A, Coppo R, Sena L M, Piccoli G
Dipartimento di Oncologia e Medicina Sperimentale, Università di Torino, Italy.
Kidney Int. 1993 May;43(5):1150-5. doi: 10.1038/ki.1993.161.
Several monocyte-macrophage functions were found to be defective in cryoglobulinemic patients. Nevertheless, monocytes actively phagocytizing cryoglobulins have been frequently found in kidney specimens from these patients. Whether subsequent degradation of the ingested immune material is effective, however, is still unknown. Monocytes from eight cryoglobulinemic patients (4 with active disease and associated nephritis and 4 inactive cases without nephritis) and eight normal controls of same sex and similar age were analyzed. Monocytes from patients with active cryoglobulinemia and associated nephritis were found to be able to ingest, but unable to catabolize, cryoglobulins, as shown by electron microscopy using gold-labeled goat IgG to human IgG and IgM in 18-hour cultured suspensions. Synthesis and maturation of monocyte cathepsin D, one of the most important lysosomal proteases, were analyzed in the same subjects. Purified monocytes were cultured in presence or absence of cryoglobulins for 18 hours at 37 degrees C in RPMI medium and labeled with 35S-methionine. The various forms of cathepsin D were separated by electrophoresis and visualized by fluorography. Results from cultures of monocytes from clinically active cryoglobulinemic patients with nephritis suggest that intracellular transport of newly synthesized cathepsin D was impaired and the release into the medium of precursor polypeptides of the enzyme enhanced in each experimental condition. Since procathepsin D is susceptible to activation in pathologic conditions lowering local pH (such as in inflamed tissues), these data suggest that monocytes from patients with active cryoglobulinemia and associated nephritis have a propensity to exert phlogistic effects via secretion of procathepsin D in tissues.
在冷球蛋白血症患者中，发现几种单核细胞 - 巨噬细胞功能存在缺陷。然而，在这些患者的肾脏标本中经常发现单核细胞积极吞噬冷球蛋白。然而，摄入的免疫物质随后的降解是否有效仍不清楚。分析了8例冷球蛋白血症患者（4例患有活动性疾病及相关肾炎，4例无肾炎的非活动性病例）和8例年龄和性别相仿的正常对照者的单核细胞。通过在18小时培养悬液中使用金标记的山羊IgG针对人IgG和IgM的电子显微镜观察发现，患有活动性冷球蛋白血症及相关肾炎的患者的单核细胞能够摄取但无法分解代谢冷球蛋白。在同一受试者中分析了单核细胞组织蛋白酶D（最重要的溶酶体蛋白酶之一）的合成和成熟情况。将纯化的单核细胞在含有或不含有冷球蛋白的情况下于37℃在RPMI培养基中培养18小时，并用35S - 蛋氨酸标记。组织蛋白酶D的各种形式通过电泳分离并用荧光自显影法可视化。来自患有肾炎的临床活动性冷球蛋白血症患者的单核细胞培养结果表明，新合成的组织蛋白酶D的细胞内转运受损，并且在每种实验条件下该酶的前体多肽向培养基中的释放增加。由于组织蛋白酶原D在降低局部pH的病理条件下（如在炎症组织中）易被激活，这些数据表明，患有活动性冷球蛋白血症及相关肾炎的患者的单核细胞倾向于通过在组织中分泌组织蛋白酶原D发挥炎症作用。
