Elevated Ferritin Concentration Research Articles

Association of elevated mid-pregnancy maternal plasma ferritin concentrations and triglyceride concentrations with the risk of gestational diabetes mellitus: A prospective cohort study.

Ferritin levels are well known to be associated with gestational diabetes mellitus (GDM). However, the association of the combination of ferritin and triglyceride (TG) levels in early mid-pregnancy with GDM has not been studied in depth. We investigated the independent and combined relationships of plasma ferritin and TG concentrations with the risk of GDM as well as the mediation effect of TG on ferritin. We analysed 2071 pregnant women from the Tongji Maternal and Child Health Cohort who had their plasma ferritin and TG concentrations measured at 11-20weeks of gestation. Associations between ferritin and TG concentrations and GDM risk were estimated using multivariable logistic regression models. Youden's index was calculated to find the cut-off values of ferritin and TG by ROC curve analysis. The mediation effect of the TG concentration on the ferritin level with GDM risk was explored by a mediation analysis. A total of 264 (12.3%) participants developed GDM. The median and IQR of ferritin was 53.9 (30.5-92.7) ng/mL. After adjusting for potential confounders, the relative risks (RRs) and 95% confidence intervals of GDM were 2.19 (1.42, 3.39) for ferritin and 2.02 (1.37, 2.97) for TG. The adjusted RR for combination was 2.40 (1.62, 3.55). Moreover, we found that the TG concentration mediated 15.0% of the total effect of the ferritin concentration on the risk of GDM. Women with a combination of both high plasma ferritin (˃55.7ng/mL) and high TG (˃1.9mmoL/L) were at the highest risk of GDM. Additionally, we have revealed for the first time that an elevated maternal TG concentration in early pregnancy mediates the relationship between ferritin concentration and GDM risk. This trial is registered at https://ClinicalTrials.gov as NCT03099837.

Association between maternal plasma ferritin concentration, iron supplement use, and the risk of gestational diabetes: a prospective cohort study

The association between iron supplementation and gestational diabetes mellitus (GDM) is still inconclusive, and this association has not been extensively studied in relation to plasma ferritin in the early second trimester. We aimed to prospectively examine the independent and combined associations of plasma ferritin concentrations and iron supplement use with GDM. We studied 2117 women from the Tongji Maternal and Child Health Cohort in Wuhan, China. Plasma ferritin around 16weeks' gestation was measured by ELISA kits and information on iron supplement use was collected by questionnaires. GDM was diagnosed by a 75-g oral-glucose-tolerance test (OGTT) at 24-28 weeks' gestation. A log-Poisson regression model was used to estimate the RR of GDM associated with plasma ferritin and iron supplementation. The median and IQR of plasma ferritin was 52.1 (29.6-89.9) ng/mL, and 863 (40.8%) participants reported use of iron supplements during the second trimester. A total of 219 (10.3%) participants developed GDM. Adjusted RRs (95% CIs) for GDM across increasing quartiles of plasma ferritin were 1.00 (reference), 2.14 (1.37, 3.34), 2.03 (1.30, 3.19), and 2.72 (1.76, 4.21), respectively. After adjustment, supplemental iron ≥60 mg/d during the second trimester was associated with an increased risk of GDM compared with nonusers (RR: 1.37; 95% CI: 1.02, 1.84). Both elevated plasma ferritin concentrations in the early second trimester and use of ≥60 mg/d of supplemental iron during pregnancy are independently associated with increased risk of GDM. Further clinical trials with precision nutrition approaches considering both baseline iron status and supplement use are needed to evaluate the benefits and risks of iron supplementation during pregnancy.

Adult-onset Still's disease after mRNA COVID-19 vaccine.

Adult-onset Still's disease after mRNA COVID-19 vaccine.

Impact of ferritin serum concentration on survival in children with acute leukemia: a long-term follow-up

Introduction: Nowadays, a significant number of children with acute leukemia can be cured. Iron overload, related to blood transfusions and its long-term complications, remains a problem. Elevated ferritin concentration is often observed in this group. The aim of this study was to evaluate the prognostic value of serum ferritin on long-term outcomes in children treated for acute leukemia. Material: We studied 71 patients treated for acute lymphoblastic (ALL) or myeloblastic (AML) leukemia between 2005 and 2011. Serum ferritin concentration, serum transaminases activity, lactic dehydrogenase and C-reactive protein levels (CRP) were analysed. Serum ferritin >1,000 µg/L was considered to be a marker of iron overload. Results: Thirty-seven patients (52.1%) had iron overload. Ferritin serum concentration correlated with alanine aminotranferase activity ( p =0.001) and CRP concentration ( p =0.012). A total of 19 (26.76%) patients died during follow-up. Ferritin level was higher in patients with AML vs. ALL. There was a significant difference in long-term outcomes with respect to high ferritin concentrations, both in patients undergoing haematopoietic cell transplantation (HCT) and in the non-HCT group. Conclusions: In both groups, patients with higher ferritin concentrations had worse overall and event-free survivals and a higher relapse incidence. Ferritin concentration >1,000 µg/L was the strongest determinant of long-term treatment outcome. Ferritin serum concentration >1,000 µg/L is an adverse prognostic marker of survival in children with acute leukemia treated with chemotherapy with or without HCT.

Hemophagocytic lymphohistiocytosis in adults: collaborative analysis of 137 cases of a nationwide German registry

PurposeHemophagocytic lymphohistiocytosis (HLH) is a severe hyperinflammatory syndrome emerging from a deregulated immune response due to various triggers. In adults, systematic data are sparse, which is why recommendations on diagnosis and management have been adopted from pediatric guidelines. A nationwide clinical registry with associated consulting service as collaborative initiative of HLH-specialized pediatricians and hematologists was initiated to better characterize HLH in adults.MethodsPatients with proven or suspected HLH were registered by 44 institutions. Both HLH-2004 diagnostic criteria and the HScore (www.saintantoine.aphp.fr/score/) were used to confirm HLH diagnosis. Data referring to underlying disease, treatment, outcome, clinical presentation and laboratory findings were recorded.ResultsThe study included 137 patients and provides the first systematic data on adult HLH in Germany. Median age was 50 years with a wide range (17–87 years), 87 patients (63.5%) were male. Most common triggering diseases were infections in 61 patients (44.5%) and malignancies in 48 patients (35%). Virtually all patients had elevated ferritin concentrations, and 74% had peak concentrations greater than 10,000 µg/l. At time of analysis, 67 of 131 patients (51%) had died. Patients with malignancy-associated HLH had the shortest median survival (160 days), however no statistically significant difference between subgroups was observed (p = 0.077). Platelets under 20*109/l and low albumin concentrations (< 20 g/l) were associated with poor overall and 30-day survival.ConclusionClose multidisciplinary case consultation and cooperation is mandatory when treating adult HLH patients. Early contact with reference centers is recommended, especially in relapsing or refractory disease.

Association of serum ferritin with metabolic syndrome in eight cities in China.

ObjectiveThis study aims to evaluate the cross‐sectional association of serum ferritin (SF) and the risk of metabolic syndrome (MetS) and its components among adults in eight cities in China.MethodsSubjects were recruited using a combination of systematic cluster random sampling and purposive sampling in eight cities in China. The sociodemographic characteristics, data of lifestyle factors, self‐reported disease history, and 24‐hr dietary intake were obtained using a validated questionnaire. Anthropometry was performed, and fasting blood was collected to test the SF, fasting blood glucose (FBG), insulin, high‐sensitivity C‐reactive protein (hs‐CRP), triglycerides (TG), and cholesterols. Logistic and linear regression analyses were conducted to investigate the associations, adjusting for age, city level, smoking, drinking, weekly moderate‐to‐vigorous activity, dietary factors, hs‐CRP, and BMI.ResultsSerum ferritin level is positively correlated with total cholesterol, TG, FBG, HOMA‐IR, and hs‐CRP after adjusting for age and BMI. The odds ratio (OR) for MetS in the highest quartile of SF was 2.23 (1.32, 3.77) after adjusting for men, compared with the lowest quartile. An elevated ferritin concentration was significantly related to hypertriglyceridemia (p < .001) and elevated glucose (p = .013) among men, but not among women. Furthermore, compared with Q1, the OR for insulin resistance in the ferritin Q4 group was 3.08 (1.50, 6.32) among men and 1.96 (1.19, 3.24) among women.ConclusionA positive association between elevated SF and MetS and its components including hypertriglyceridemia and elevated glucose was found in multivariate analyses among men, and SF levels are independently associated with IR.

Hepatology Basic Science

Hepatology Basic Science

Decreased VEGF Level Is Associated with Elevated Ferritin Concentration in Bronchoalveolar Lavage Fluid of Children with Interstitial Lung Diseases

Background: A decreased level of vascular endothelial growth factor (VEGF) was previously described in bronchoalveolar lavage fluid (BALF) of adults with interstitial lung diseases (ILD) due to bronchial epithelial cell apoptosis and its proteolytic degradation. Elevated intrapulmonary ferritin was produced by alveolar cells that promoted oxidative injury in such patients. Objectives: In this study, we analyzed the concentrations of VEGF and ferritin in BALF samples of ILD children and studied the relationship between their levels and the degree of inflammation. Methods: BALF and serum concentration of VEGF as well as ferritin and albumin in BALF samples were measured using enzyme-linked immunosorbent assay in children with idiopathic interstitial pneumonia (n = 16), hypersensitivity pneumonitis (n = 11) and idiopathic pulmonary hemosiderosis (n = 3). Twenty-four age- and gender-matched subjects with suspicious foreign body aspiration served as a control group. Results: VEGF per albumin levels in BALF were significantly decreased in ILD children compared to controls (1,075 [784-1,415] pg/mg albumin vs. 2,741 [1,131-4,660] pg/mg albumin, p = 0.0008). These values showed a significant negative correlation with inflammatory markers of total immune cell count in BALF (r = -0.411, p = 0.002) and serum C-reactive protein (r = -0.367, p = 0.006). Although serum VEGF was augmented in ILD children versus controls, no difference was observed among the ILD groups. In addition, BALF ferritin/albumin level (688 [188-1,571] ng/mg albumin vs. 256 [178-350] ng/mg albumin, p = 0.022) was significantly higher than normal in ILD individuals, especially in idiopathic pulmonary hemosiderosis. Conclusion: Depressed VEGF and increased ferritin in BALF may reflect the severity of chronic pulmonary inflammation in altered respiratory epithelium of childhood ILD.

Association of serum ferritin concentrations with prevalence of prediabetes, type 2 diabetes mellitus, and metabolic syndrome in a Chinese population from Sichuan

Body iron stores reflected by serum ferritin levels have been implicated in many chronic diseases. We investigated associations between serum ferritin concentrations and the risk of prediabetes, type 2 diabetes mellitus (T2DM), and metabolic syndrome (MetS) in a Chinese population. For a cross-sectional study, 3040 subjects were recruited from three communities in Sichuan. Subjects were grouped by prediabetes or T2DM status, or components of MetS. Subjects with prediabetes were classified as having impaired fasting glucose (IFG), impaired glucose tolerance (IGT), or both (IFG + IGT). The odds ratios, assessed by gender, for the associations between serum ferritin concentration and prediabetes, T2DM, and MetS were calculated using multivariate logistic regression. The prevalence of IGT, IFG + IGT, T2DM, and MetS in the highest quartile of ferritin concentrations was higher than those in the lowest quartile, in both genders. In women, the adjusted odds ratios of IGT, IFG + IGT, T2DM, and MetS were higher in the highest ferritin quartile than the lowest; in men, only that of IFG + IGT was higher. In both genders, high ferritin levels were associated with higher odds ratios of hypertriglyceridemia and hyperglycemia, components of MetS. IGT, IFG + IGT, T2DM, and MetS were more common in the highest ferritin quartile for both genders. Elevated ferritin concentrations were associated with an increased risk for IGT and IFG + IGT in prediabetes, T2DM, and MetS, especially in women.

Gender differences in associations of serum ferritin and diabetes, metabolic syndrome, and obesity in the China Health and Nutrition Survey.

This study examines gender differences in associations of serum ferritin and diabetes, metabolic syndrome (MetS), and obesity in Chinese. Based on a nationwide, population-based China Health and Nutrition survey this study included 8564 men and women aged 18 years or older. Anthropometric and fasting blood glucose, insulin, lipids, ferritin, and transferrin data were collected. Ferritin concentrations were higher in men than women (201.55 ± 3.6 versus 80.46 ± 1.64 ng/mL, p < 0.0001). The prevalences of MetS, diabetes, obesity, and overweight were 8.05, 8.97, 4.67, 25.88% among men and 14.23, 6.58, 5.81, 26.82% among women, respectively. Elevated ferritin concentrations were associated with higher body mass index, waist circumference, lipids, insulin, glucose (all p < 0.0001). Serum ferritin concentrations increased gradually with aging among women. The inverted U-shaped association between serum ferritin and age was observed among men. Elevated concentration of ferritins were significantly related with higher risk of MetS (p < 0.0001), obesity (p = 0.010), overweight (p < 0.0001), and diabetes (p < 0.0001) among men, but not among women. There was a gender difference in associations between ferritin and MetS, obesity, and diabetes in Chinese adults. Further evaluations of the variation in gender on these associations are warranted to understand the mechanisms behind gender differences.

Hypoxia induced changes in expression of proteins involved in iron uptake and storage in cultured lens epithelial cells

Hypoxia inducible factor (HIF) regulates expression of over 60 genes by binding to hypoxia response elements (HRE) located upstream of the transcriptional start sites. Many genes encoding proteins involved in iron transport and homeostasis are regulated by HIF. Expression of iron handling proteins can also be translationally regulated by binding of iron regulatory protein (IRP) to iron responsive elements (IREs) on the mRNA of ferritin chains and transferrin receptor (TfR). Lens epithelial cells (LEC) function in a low oxygen environment. This increases the risk of iron catalyzed formation of reactive oxygen species (ROS) and oxidative cell damage. We examined changes in expression of ferritin (iron storage protein) and Tf/TfR1 (iron uptake proteins) in LEC cultured under hypoxic conditions. Ferritin consists of 24 subunits of two types, heavy (H-chain) and light (L-chain) assembled in a cell specific ratio. Real-time PCR showed that 24 h exposure to hypoxia lowered transcription of both ferritin chains by over 50% when compared with normoxic LEC. However it increased the level of ferritin chain proteins (20% average). We previously found that 6 h exposure of LEC to hypoxia increased the concentration of cytosolic iron which would stimulate translation of ferritin chains. This elevated ferritin concentration increased the iron storage capacity of LEC. Hypoxic LEC labeled with 59FeTf incorporated 70% more iron into ferritin after 6 h as compared to normoxic LEC. Exposure of LEC to hypoxia for 24 h reduced the concentration of TfR1 in cell lysates. As a result, hypoxic LEC internalized less Tf at this later time point. Incorporation of 59Fe into ferritin of hypoxic LEC after 24 h did not differ from that of normoxic LEC due to lower 59FeTf uptake. This study showed that hypoxia acutely increased iron storage capacity and lowered iron uptake due to changes in expression of iron handling proteins. These changes may better protect LEC against oxidative stress by limiting iron-catalyzed ROS formation in the low oxygen environment in which the lens resides.

Elevated Serum Ferritin Level Is Associated with the Incident Type 2 Diabetes in Healthy Korean Men: A 4 Year Longitudinal Study

BackgroundElevated ferritin concentration has been implicated in the etiology of type 2 diabetes. Accumulating evidence, mostly from studies conducted on western populations, has demonstrated a strong association between the elevated ferritin concentrations and incident type 2 diabetes. In Asian populations, however, the longitudinal studies investigating the association of elevated serum ferritin levels and type 2 diabetes are lacking. In present study, we aimed to determine whether elevated serum ferritin levels are related to the incident type 2 diabetes in healthy Korean men.Methodology/Principal FindingsThis 4 year longitudinal observational study was conducted at the Asan Medical Center, Seoul, Republic of Korea. The study population consisted of 2,029 men without type 2 diabetes who underwent routine health examination in 2007 (baseline) and 2011 (follow-up). Baseline serum ferritin concentrations were measured by chemiluminescent two-site sandwich immunoassay. In multiple-adjusted model, the relative risk (RR) for incident type 2 diabetes was significantly higher in highest compared with the lowest ferritin quartile category, even after adjusting for confounding variables including homeostasis model assessment of insulin resistance (RR = 2.17, 95% confidence interval 1.27–3.72, P for trend = 0.013).Conclusions/SignificanceThese results demonstrated that elevated level of serum ferritin at baseline was associated with incident type 2 diabetes in an Asian population.

Increased Ferritin Concentrations Correlate with Insulin Resistance in Female Type 2 Diabetic Patients

Aims: Iron overload identified by elevated ferritin concentrations has been implicated in risks of altered glucose metabolism and diabetic complications. The relationship between ferritin and insulin resistance in different gender and ethnicities remains uncertain; this study aimed to investigate it using homeostasis model assessment (HOMA-IR), and to explore whether it is gender-specific. Methods: A total of 524 type 2 diabetic patients were selected cross-sectionally from a cohort participating in a diabetic control study in Taiwan. Result: Overall, tertiles of ferritin were significantly and dose-dependently associated with elevated fasting plasma glucose, hemoglobin A1c, high-sensitivity C-reactive protein, HOMA-IR levels as well as Western dietary pattern scores generated by factor analysis (all p trend <0.05). Stratified by gender, a 1-tertile ferritin increase significantly correlated with a 0.241-unit increase in HOMA-IR (beta = 0.241, p = 0.001) in female diabetes, but not in male diabetes (beta = 0.072, p = 0.232), after adjusting for demographic, dietary, clinical and inflammatory factors. Conclusion: Iron overload, which produces elevated levels of ferritin, may augment insulin resistance in female but not in male type 2 diabetes. Longitudinal studies are warranted to establish relationships between iron stores and diabetes development in men and women of different ethnicities.

The relationship between serum ferritin and metabolic syndrome in healthy Korean men

Elevated serum ferritin levels have been reported to be associated with several metabolic disorders. We investigated the relationship between serum ferritin level and metabolic syndrome and its components in healthy Korean men. In this cross-sectional study, serum ferritin level and metabolic syndrome and its components were measured from 18 581 men from January to December in 2008. The presence of metabolic syndrome was determined according to the most recent consensus report of the National Cholesterol Education Program's Third Adult Treatment Panel. Logistic regression models were applied to examine the relationship between the serum ferritin level and the metabolic syndrome and its components. After adjusting for clinical covariates, the odds ratio and 95% confidence intervals of metabolic syndrome with respect to Q2, Q3 and Q4 were 1.34 (1.14-1.57), 1.49 (1.24-1.70) and 1.99 (1.70-2.33), respectively (p for trend < 0.001). The multivariable-adjusted model also showed a significantly graded relationship between individual components of metabolic syndrome and the quartile groups of serum ferritin. In this study, elevated ferritin concentration is independently associated with metabolic syndrome and its components among healthy Korean men.

Serum Ferritin in Healthy Women and Breast Cancer Patients

Serum Ferritin in Healthy Women and Breast Cancer PatientsSerum tumor markers are important tools in managing patients with breast cancer. Currently used CA 15-3 and CEA have found their clinical application particularly in the follow-up of patients with advanced disease. Ferritin belongs to a group of other molecules of potential interest to clinicians whose concentration is also altered in sera of patients with breast tumors. In this study the serum ferritin concentration was estimated in the sera of breast cancer patients before initial surgical treatment or those with advanced disease, and compared to healthy women as control. Ferritin level was measured by an immunoradiometric assay. The aim was to asses whether the serum ferritin concentration was altered in breast cancer and whether it could be related to progression of the disease. In healthy women, a statistically significant difference (p&lt;0.05) in ferritin concentration was observed between premenopausal and postmenopausal women. In both breast cancer groups ferritin levels were higher than in healthy premenopausal women (both p&lt;0.05). In patients with advanced disease, ferritin was further elevated (p&lt;0.05) compared to preoperative levels in the patient group undergoing initial surgical treatment. These results indicate that an elevated ferritin concentration in the serum of younger women could serve as an additional parameter in breast cancer diagnosis and staging.

Exchange Transfusion as a Possible Therapy for Neonatal Hemochromatosis

Exchange Transfusion as a Possible Therapy for Neonatal Hemochromatosis

Iron and Ferritin Concentrations in Exhaled Breath Condensate of Children with Asthma

Maintenance of iron homeostasis is of utmost importance for the respiratory system physiology and pathophysiology. Local iron deficiency or accumulation may result in particular respiratory function impairment. The aim of the present study was to find out whether iron and ferritin could be determined in exhaled breath condensate (EBC) of healthy children and children with asthma. Oxidative stress was verified by determination of EBC superoxide dismutase (SOD) activity, and the airway inflammatory process by determination of exhaled nitric oxide (FENO). EBC was collected from 39 children (22 healthy children as a control group and 17 asthmatics) using an EcoScreen condenser. Iron, ferritin, and SOD were determined on optimization and validation for low concentrations. In comparison with a control group, asthma patients had a statistically significantly lower iron concentration (p = 0.0001) and higher SOD catalytic activity (p = 0.0160), with no significant difference in ferritin levels (p = 0.5252), although percentile values indicated elevated ferritin concentration in about half of asthma patients. FENO values were significantly higher in the asthma group (p = 0.0047). This preliminary study demonstrated the possibility of determining iron and ferritin concentrations and SOD activity in EBC, and a significant difference in EBC iron and SOD between asthma patients and healthy children.

Elevated Concentrations of Liver Enzymes and Ferritin Identify a New Phenotype of Insulin Resistance: Effect of Weight Loss After Gastric Banding

Several studies have associated elevated liver enzymes (LFTs), obesity, and type 2 diabetes (T2DM), and a link has been established between insulin resistance (IR) and elevated ferritin concentrations. We examined the relationship between LFTs, ferritin, and IR in morbid obese subjects and the effect of weight loss after bariatric surgery. We measured liver enzymes, ferritin, insulin resistance, and glucose tolerance (by OGTT) in 159 morbid obese subjects (BMI = 44.4 +/- 0.4 kg/m(2)) at baseline, 6 months and 1 year after laparoscopic-adjustable-gastric banding (LAGB). Subjects were divided in two groups: increased LFTs (ALT > 30; AST/ALT < 1) vs. normal LFTs. A large proportion of morbid obese subjects had increased LFTs (44%) which were associated with increased IR and ferritin, suggesting potential liver disease. A majority of the morbidly obese with increased LFTs, IGT, and T2DM, were male and had almost double ferritin concentrations, strongly correlated with ALT (r = 0.43, p < 0.0001). Both ferritin and ALT correlated with waist circumference and IR. One year after, LAGB glucose tolerance improved, LFTs and IR were reduced; ferritin did not change significantly, but was still correlated with IR. Ferritin may be an additional useful marker for more severe hepatic IR.

Ferritin Concentrations, Metabolic Syndrome, and Type 2 Diabetes in Middle-Aged and Elderly Chinese

Elevated ferritin concentrations frequently cluster with well-established risk factors of diabetes including obesity, metabolic syndrome, chronic inflammation, and altered circulating adipokines. Few studies, however, have systematically evaluated the effect of these risk factors on ferritin-diabetes association, particularly in Chinese populations. We aimed to investigate, in a middle-aged and elderly Chinese population, whether elevated ferritin concentrations are associated with higher risk of metabolic syndrome and type 2 diabetes and to what extent the associations were influenced by obesity, inflammation, and adipokines. We conducted a population-based, cross-sectional survey of 3,289 participants aged 50-70 yr in Beijing and Shanghai in 2005. Fasting plasma ferritin, glucose, insulin, lipid profile, glycohemoglobin, inflammatory markers, adipokines, and dietary profile were measured. Median ferritin concentrations were 155.7 ng/ml for men and 111.9 ng/ml for women. After multiple adjustment, the odds ratios (ORs) were substantially higher for type 2 diabetes (OR 3.26, 95% confidence interval 2.36-4.51) and metabolic syndrome [OR 2.80 (95% confidence interval 2.24-3.49)] in the highest ferritin quartile compared with those in the lowest quartile. These associations remained significant after further adjustment for dietary factors, body mass index, inflammatory markers, and adipokines. Elevated circulating ferritin concentrations were associated with higher risk of type 2 diabetes and metabolic syndrome in middle-aged and elderly Chinese independent of obesity, inflammation, adipokines, and other risk factors. Our data support the crucial role of iron overload for metabolic diseases, even in a country with relatively high prevalence of iron deficiency.

Oxidant Generation Promotes Iron Sequestration in BEAS-2B Cells Exposed to Asbestos

Lung injury after asbestos exposure is associated with an oxidative stress that is catalyzed by iron in the fiber matrix, complexed to the surface, or both. We tested the hypothesis that the cellular response to asbestos includes the transport and sequestration of this iron through (1) generation of superoxide for ferrireduction, (2) up-regulation of divalent metal transporter-1 (DMT1) for intracellular transport of Fe2+, and (3) increased production of cellular ferritin where the metal is stored in a catalytically less reactive state. BEAS-2B cells with normal and elevated Cu,Zn superoxide dismutase (SOD) expression were employed for in vitro investigations. After exposure of these cells to asbestos, we demonstrated by fluorescence methodology a significantly increased generation of SOD with ferrireductive capacity. Fiber exposure also increased DMT1 protein and mRNA expression in the BEAS-2B cells. Incubation with asbestos elevated cellular iron and ferritin concentrations, and these responses were diminished in cells with an enhanced expression of SOD. Finally, fiber exposure increased supernatant concentrations of interleukin 8, but this inflammatory mediator was actually increased in cells with elevated SOD expression. We conclude that the response of respiratory epithelial cells to asbestos includes oxidant-mediated mechanisms to sequester catalytically active iron associated with the fiber.