The Physiological Role of Ferritin-Like Compounds in Bacteria

Iron, as the ferrous or ferric ion, is essential for the life processes of all eukaryotes and most prokaryotes; however, the element is toxic when in excess of that needed for cellular homeostasis. Ferrous ions can react with metabolically generated hydrogen peroxide to yield toxic hydroxyl radicals that in turn degrade lipids, DNA, and other cellular biomolecules. Mechanisms have evolved in living systems for iron detoxification and for the removal of excess ferrous ions from the cytosol. These detoxification mechanisms involve the oxidation of excess ferrous ions to the ferric state and storage of the ferric ions in ferritin-like proteins.

There are at least three types of ferritin-like proteins in bacteria: bacterial ferritin, bacterioferritin, and dodecameric ferritin. These bacterial proteins are related to the ferritins found in eukaryotes. The structure and physical characteristics of the ferritin-like compounds have been elucidated in several bacteria. Unfortunately, the physiological roles of the bacterial ferritin-like compounds have been less thoroughly studied. A few studies conducted with mutants indicated that ferritin-like compounds can protect bacterial cells from iron overload, serve as an iron source when iron is limited, protect the bacterial cells against oxidative stress and/or protect DNA against enzymatic or oxidative attack. There is very little information available concerning the roles that ferritin-like compounds might play in the survival of bacteria in food, water, soil, or eukaryotic host environments.     

Expression of transferrin receptors and intracellular ferritin during terminal differentiation of human monocytes

Summary Human blood monocytes when cultured on hydrophobic Teflon membranes differentiate into mature macrophages. The expression of transferrin receptors was monitored by monoclonal antibody (OKT9) binding as detected by immunperoxidase staining. Whereas monocytes were negative, an increasing percentage of macrophages, starting from day 2 in culture, labelled with the anti-transferrin receptor antibody as these cells undergo differentiation. After completion of maturation more than 90% of macrophages expressed transferrin receptors. While 90–95% of macrophages from broncho-alveolar lavage fluids labelled with the OKT9 antibody, only a minor portion of macrophages obtained from peritoneal and pleural cavities did so. In parallel, intracellular ferritin in cells of the monocyte-macrophage lineage increased from 10ng/10⁶ cells to 350–1,500ng/10⁶ cells during maturation in vitro. Alveolar macrophages proved to have the highest ferritin content which ranged from 355–8,400ng/10⁶.The results may indicate that iron uptake and storage is a function of cells at late stages of macrophage maturation and that the occurrence of surface receptors for transferrin can be regarded as differentiation dependent marker.Supported by Deutsche Forschungsgemeinschaft     

sCD163和铁蛋白在HBV相关慢加急性肝功能衰竭中的表达及其临床意义

目的：研究 HBV相关慢加急性肝功能衰竭（HBV-ACLF）患者血浆中可溶性 CD163（sCD163）和铁蛋白水平,分析其与患者病情、预后的关系。方法选择HBV-ACLF患者30例、乙型肝炎肝硬化25例、慢性乙型肝炎18例以及健康对照15例,采用ELISA方法检测血浆中 sCD163和铁蛋白水平。结果 HBV-ACLF 组血浆中 sCD163和铁蛋白水平均明显高于肝硬化组、慢性乙型肝炎组及健康对照组[sCD163：（123±43）比（76±33）、（58±19）、（35±15）ng/mL,均P＜0．05;铁蛋白：（2714±1896）比（505±722）、（833±801）、（106±58）ng/mL,均P＜0．05]。肝衰竭发展到晚期时sCD163和铁蛋白水平均较早、中期明显增高[sCD163：（162±44）比（104±40）、（108±24）ng/mL,均P＜0．05）;铁蛋白：（4154±2122）比（1746±1047）、（2416±1713）ng/mL,均P＜0．05]。HBV-ACLF死亡组中sCD163和铁蛋白水平均高于存活组[sCD163：（140±42）比（101±36）mg/mL,（t＝-2．719,P＝0．01）;铁蛋白：（3568±2007）比（1598±957）ng/mL,（t＝-3．547,P＝0．001）]。经受试者工作特征曲线（ROC）分析,sCD163、铁蛋白评估 HBV-ACLF患者3个月内死亡所对应的曲线下面积（AUC）分别为0．803、0．844。结论 sCD163和铁蛋白可作为 HBV-ACLF病情严重程度及预后评估的重要参考指标。     

Iron metabolism imbalance at the time of listing increases overall and infectious mortality after liver transplantation

BACKGROUND Liver transplantation(LT) is the best treatment for patients with liver cancer or end stage cirrhosis, but it is still associated with a significant mortality. Therefore identifying factors associated with mortality could help improve patient management. The impact of iron metabolism, which could be a relevant therapeutic target, yield discrepant results in this setting. Previous studies suggest that increased serum ferritin is associated with higher mortality.Surprisingly iron deficiency which is a well described risk factor in critically ill patients has not been considered.AIM To assess the impact of pre-transplant iron metabolism parameters on posttransplant survival.METHODS From 2001 to 2011, 553 patients who underwent LT with iron metabolism parameters available at LT evaluation were included. Data were prospectively recorded at the time of evaluation and at the time of LT regarding donor and recipient. Serum ferritin(SF) and transferrin saturation(TS) were studied as continuous and categorical variable. Cox regression analysis was used to determine mortality risks factors. Follow-up data were obtained from the local and national database regarding causes of death.RESULTS At the end of a 95-mo median follow-up, 196 patients were dead, 38 of them because of infections. In multivariate analysis, overall mortality was significantly associated with TS 75% [HR: 1.73(1.14; 2.63)], SF 100 μg/L [HR: 1.62(1.12;2.35)], hepatocellular carcinoma [HR: 1.58(1.15; 2.26)], estimated glomerular filtration rate(CKD EPI Cystatin C) [HR: 0.99(0.98; 0.99)], and packed red blood cell transfusion [HR: 1.05(1.03; 1.08)]. Kaplan Meier curves show that patients with low SF( 100 μg/L) or high SF( 400 μg/L) have lower survival rates at 36 mo than patients with normal SF(P = 0.008 and P = 0.016 respectively). Patients with TS higher than 75% had higher mortality at 12 mo(91.4% ± 1.4% vs 84.6% ±3.1%, P = 0.039). TS 75% was significantly associated with infection related death [HR: 3.06(1.13; 8.23)].CONCLUSION Our results show that iron metabolism imbalance(either deficiency or overload)is associated with post-transplant overall and infectious mortality. Impact of iron supplementation or depletion should be assessed in prospective study.     

急性胰腺炎血清中ICAM-1、SF水平变化及临床意义

目的 探讨血清中细胞间黏附分子-1(ICAM-1)、铁蛋白(SF)水平变化对急性胰腺炎严重程度评估的临床意义。方法 收集内蒙古医科大附属医院(2014年-2018年)急性胰腺炎(Acute pancreatitis AP)患者73例作为研究对象,其中轻症急性胰腺炎组43例( MAP组,n=43),重症急性胰腺炎组30例(SAP组,n=30)。在发病第24h、48h、72h和96h分别对所有患者进行ICAM-1、SF检测,同时行AP严重程度Ranson评分和CT严重程度指数(CTSI)评分。对2组患者不同时间段ICAM-1、SF、Ranson评分和CTSI评分进行比较,同时进行ICAM-1、SF与Ranson评分和CTSI评分的相关性分析。结果 (1)发病第24h,MAP的ICAM-1、SF平均值(29.68 ± 8.04 vs16.77±4.37)、( 908.7±158.6 vs719.6±208.5)均较SAP组低,有显著性差异(P均＜0.001)。两组患者发病第24h血清中ICAM-1、SF水平明显高于其入院后24h、72-96h(P均＜0.001)。患者入院后Ranson评分和CTSI评分均与ICAM-1、SF水平密切相关(r均＞0.9)。结论 患者血清ICAM-1、SF水平及其变化对于急性胰腺炎严重程度及预后具有预估作用。     

Aging is an organ-specific process: changes in homeostasis of iron and redox proteins in the rat

Organ-specific changes of iron- and redox-related proteins occur with age in the rat. Ferritin, the major iron storage and detoxifying protein, as well as the proteins of the methionine-centered redox cycle (MCRC) were examined in old and young animals, and showed organ-dependent changes. In spleens and livers of aged rats, ferritin (protein) levels were greater than in young ones, and their iron saturation increased, rendering higher ferritin-bound iron (FtBI). Iron saturation of the ferritin molecule in the tongues and sternohyoids of old rats was lower but ferritin level was higher than in young rats, resulting in increased FtBI with age. Ferritin level in the esophagus of older rats was lower than in young rats but its molecular iron content higher thus the total FtBI remained the same. In the larynx, both ferritin and its iron content were the same in young and old animals. MCRC proteins were measured in livers and spleens only. With aging, methionine sulfoxide reductase A and B (MsrA and MsrB) levels in livers and spleens decreased. Thioredoxin1 (Trx) and Trx-reductase1 were elevated in old spleens, but reduced in livers. Aged spleens showed reduced Msr isozyme activity; but in the liver, its activity increased. mRNA changes with age were monitored and found to be organ specific. These organ-specific changes could reflect the different challenges and the selective pathways of each organ and its resultant capacity to cope with aging.     

Intravenous iron sucrose for restless legs syndrome in pregnant women with low serum ferritin

We report on two pregnant women who either had de novo restless legs syndrome (RLS) or had marked enhancement of preexisting RLS symptoms during pregnancy. Both patients had ferritin values <50 μg/L at baseline. The patients had relevant sleep disorders and daytime symptoms caused by RLS. The women were treated in an open paradigm with intravenous iron sucrose. A few weeks after therapy, both patients experienced a significant reduction or even remission of RLS symptoms. Their quality of life and sleep substantially improved and no treatment-related adverse effects were observed. According to our initial experience, intravenous iron sucrose administration appears to be an effective therapy in RLS patients with low ferritin values during pregnancy.     

Characteristics of a Specific Radioimmunoassay for Measurement of Ferritin on the Surface of Peripheral Mononuclear White Blood Cells in Cancer Patients

Using ¹²⁵I-labeled rabbit anti-Hodgkin's spleen ferritin antibody (RHF), a simple radioimmunoassay has been developed for quantitation of ferritin on the surface of peripheral blood mononuclear white blood cells (PBM). This method makes use of a % specific binding determination (%SP) by measuring the amount of ¹²⁵I-labeled RHF bound to 1 × 10⁶ PBM in the presence and absence of soluble ferritin. To standardize this procedure, artificial ferritin positive control cells were prepared by covalently coupling ferritin to cultured acute lymphoblastic luekemia cells. These cells were tested on a daily basis in parallel with patient PBM's to ensure inter and intra-assay precision and remained stable for over two years. Characteristics of ¹²⁵I-labeled RHF binding to control and patient PBM's were evaluated to determine the specificity of interaction and optimum binding parameters. %SP was linear in the range of 1 × 10⁵ - 1 × 10⁶ PBM's and was progressively inhibited by graded concentrations of soluble ferritin. F(ab')₂ preparations of RHF were equally as effective as intact RHF in blocking ¹²⁵I-labeled RHF binding confirming that ¹²⁵I-labeled RHF was not binding non-specifically to PBM Fc receptors. Additional experiments describing kinetics and methods of standardization of new lots of ¹²⁵I-labeled RHF are also described.