Iron Acquisition by the Reticuloendothelial System

Author(s):  
Günter Weiss
2020 ◽  
Author(s):  
Goran Mohammad ◽  
Athena Matakidou ◽  
Peter A Robbins ◽  
Samira Lakhal-Littleton

ABSTRACTThe hepcidin/ferroportin axis controls systemic iron homeostasis by regulating iron acquisition from the duodenum and the reticuloendothelial system, respective sites of iron absorption and recycling. Ferroportin is also abundant in the kidney, where it has been implicated in iron reabsorption. However, it remains unknown whether hepcidin regulates ferroportin-mediated iron reabsorption and whether such regulation is important for systemic iron homeostasis. To address these questions, we generated a novel mouse model with an inducible renal-tubule specific knock-in of fpnC326Y, which encodes a hepcidin-resistant FPNC326Y. Under iron-replete conditions, female mice harbouring this allele had lower renal iron content and higher serum and liver iron levels than controls. Under conditions of excess iron availability, male and female mice harbouring this allele had greater liver iron overload, but lower renal iron overload relative to controls. In addition, hemochromatosis mice harbouring a ubiquitous knock-in of fpnC326Y did not develop renal iron overload otherwise seen in the setting of excess iron availability. These findings are the first formal demonstration that hepcidin regulates ferroportin-mediated iron reabsorption. They also show that loss of this regulation contributes to liver iron overload while protecting the kidney in the setting of hemochromatosis. Our findings have important implications. First, they indicate that targeting the hepcidin/ferroportin axis for treating iron overload disorders will inhibit iron reabsorption and increase renal iron content. Second, they suggest that inhibition of iron reabsorption by raised hepcidin in chronic inflammatory conditions contributes to iron deficiency and that parenteral iron supplementation in this setting may cause renal iron overload.


1986 ◽  
Vol 25 (01) ◽  
pp. 15-18 ◽  
Author(s):  
M. Luostarinen ◽  
M Vorne ◽  
T. Lantto

Summary 99mTc tin colloid accumulated in the lungs in 102 patients during liver imaging both in malignant and benign diseases. The percentage of neoplastic diseases increased when the lung uptake became greater and only patients with malignant final diagnosis had marked lung uptake. Abnormal liver image was seen only in 23%, which disagrees highly with some earlier findings on a rather small number of patients. The cause of increased lung uptake was suggested to be the activation of the reticuloendothelial system (RES) by disease. The activation of the RES was stronger in malignant than in benign diseases. Some type of regional stimulation of the RES was suggested as being due to the location of the disease and both malignant and benign diseases of the chest region stimulated the pulmonary part of the RES more than other parts of the RES.


1969 ◽  
Vol 22 (03) ◽  
pp. 496-507 ◽  
Author(s):  
W.G van Aken ◽  
J Vreeken

SummaryCarbon particles cause platelet aggregation in vitro and in vivo. Prior studies established that substances which modify thrombocyte aggregation also influence the rate at which carbon is cleared from the blood.This study was performed in order to elucidate the mechanism by which the carbon-platelet aggregates specifically accumulate in the RES.Activation of fibrinolysis by urokinase or streptokinase reduced the carbon clearance rate, probably due to generated fibrinogen degradation products (FDP). Isolated FDP decreased the carbon clearance and caused disaggregation of platelets and particles in vitro. Inhibition of fibrinolysis by epsilon-amino-caproic acid (EACA), initially accelerated the disappearance of carbon and caused particle accumulation outside the RES, predominantly in the lungs. It is supposed that platelet aggregation and locally activated fibrinolysis act together in the clearance of particles. In the normal situation the RES with its well known low fibrinolytic activity, becomes the receptor of the particles.


Author(s):  
Azadi A. ◽  
Khazaei M. ◽  
Ashrafi H.

Cancer, an uncontrollable growth of cells, is among the leading causes of mortality and morbidity throughout the world. Malignant neoplasms are difficult to treat diseases because of their single in kind characteristics such as tissue invasion, metastasis, evading reticuloendothelial system (RES) and so forth. In recent decade polymeric nanoparticulate systems has gained special attention in drug delivery and targeting among all biocompatible nanoforms. Among these systems, chitosan-based hydrogel nanoparticles have been wildly utilized for drug delivery purposes. The usage of chitosan nanogels in cancer therapy significantly improved in recent years. The various cancers were the target of chitosan nanogels. Also, modification of other delivery systems with chitosan were much reported. The aim of this study is the review and update of the recent studies on chitosan nanogels applications in cancer therapy by focus on cancer based classification.


2020 ◽  
Vol 88 (8) ◽  
Author(s):  
Danelle R. Weakland ◽  
Sara N. Smith ◽  
Bailey Bell ◽  
Ashootosh Tripathi ◽  
Harry L. T. Mobley

ABSTRACT Serratia marcescens is a bacterium frequently found in the environment, but over the last several decades it has evolved into a concerning clinical pathogen, causing fatal bacteremia. To establish such infections, pathogens require specific nutrients; one very limited but essential nutrient is iron. We sought to characterize the iron acquisition systems in S. marcescens isolate UMH9, which was recovered from a clinical bloodstream infection. Using RNA sequencing (RNA-seq), we identified two predicted siderophore gene clusters (cbs and sch) that were regulated by iron. Mutants were constructed to delete each iron acquisition locus individually and in conjunction, generating both single and double mutants for the putative siderophore systems. Mutants lacking the sch gene cluster lost their iron-chelating ability as quantified by the chrome azurol S (CAS) assay, whereas the cbs mutant retained wild-type activity. Mass spectrometry-based analysis identified the chelating siderophore to be serratiochelin, a siderophore previously identified in Serratia plymuthica. Serratiochelin-producing mutants also displayed a decreased growth rate under iron-limited conditions created by dipyridyl added to LB medium. Additionally, mutants lacking serratiochelin were significantly outcompeted during cochallenge with wild-type UMH9 in the kidneys and spleen after inoculation via the tail vein in a bacteremia mouse model. This result was further confirmed by an independent challenge, suggesting that serratiochelin is required for full S. marcescens pathogenesis in the bloodstream. Nine other clinical isolates have at least 90% protein identity to the UMH9 serratiochelin system; therefore, our results are broadly applicable to emerging clinical isolates of S. marcescens causing bacteremia.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jing Gao ◽  
Paula J. M. van Kleeff ◽  
Ka Wan Li ◽  
Albertus H. de Boer

AbstractTo date, few phenotypes have been described for Arabidopsis 14-3-3 mutants or the phenotypes showing the role of 14-3-3 in plant responding to abiotic stress. Although one member of the 14-3-3 protein family (14-3-3 omicron) was shown to be involved in the proper operation of Fe acquisition mechanisms at physiological and gene expression levels in Arabidopsis thaliana, it remains to be explored whether other members play a role in regulating iron acquisition. To more directly and effectively observe whether members of 14-3-3 non-epsilon group have a function in Fe-deficiency adaptation, three higher order quadruple KOs, kappa/lambda/phi/chi (klpc), kappa/lambda/upsilon/nu(klun), and upsilon/nu/phi/chi (unpc) were generated and studied for physiological analysis in this study. The analysis of iron-utilization efficiency, root phenotyping, and transcriptional level of Fe-responsive genes suggested that the mutant with kl background showed different phenotypes from Wt when plants suffered Fe starved, while these phenotypes were absent in the unpc mutant. Moreover, the absence of the four 14-3-3 isoforms in the klun mutant has a clear impact on the 14-3-3 interactome upon Fe deficiency. Dynamics of 14-3-3-client interactions analysis showed that 27 and 17 proteins differentially interacted with 14-3-3 in Wt and klun roots caused by Fe deficiency, respectively. Many of these Fe responsive proteins have a role in glycolysis, oxidative phosphorylation and TCA cycle, the FoF1-synthase and in the cysteine/methionine synthesis. A clear explanation for the observed phenotypes awaits a more detailed analysis of the functional aspects of 14-3-3 binding to the target proteins identified in this study.


2021 ◽  
Vol 9 (2) ◽  
pp. 310
Author(s):  
Masayuki Hashimoto ◽  
Yi-Fen Ma ◽  
Sin-Tian Wang ◽  
Chang-Shi Chen ◽  
Ching-Hao Teng

Uropathogenic Escherichia coli (UPEC) is a major bacterial pathogen that causes urinary tract infections (UTIs). The mouse is an available UTI model for studying the pathogenicity; however, Caenorhabditis elegans represents as an alternative surrogate host with the capacity for high-throughput analysis. Then, we established a simple assay for a UPEC infection model with C. elegans for large-scale screening. A total of 133 clinically isolated E. coli strains, which included UTI-associated and fecal isolates, were applied to demonstrate the simple pathogenicity assay. From the screening, several virulence factors (VFs) involved with iron acquisition (chuA, fyuA, and irp2) were significantly associated with high pathogenicity. We then evaluated whether the VFs in UPEC were involved in the pathogenicity. Mutants of E. coli UTI89 with defective iron acquisition systems were applied to a solid killing assay with C. elegans. As a result, the survival rate of C. elegans fed with the mutants significantly increased compared to when fed with the parent strain. The results demonstrated, the simple assay with C. elegans was useful as a UPEC infectious model. To our knowledge, this is the first report of the involvement of iron acquisition in the pathogenicity of UPEC in a C. elegans model.


Gut Pathogens ◽  
2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Mahoko Ikeda ◽  
Tatsuya Kobayashi ◽  
Fumie Fujimoto ◽  
Yuta Okada ◽  
Yoshimi Higurashi ◽  
...  

Abstract Background Although Escherichia coli is the most frequently isolated microorganism in acute biliary tract infections with bacteremia, data regarding its virulence are limited. Results Information on cases of bacteremia in acute biliary tract infection in a retrospective study was collected from 2013 to 2015 at a tertiary care hospital in Japan. Factors related to the severity of infection were investigated, including patient background, phylogenetic typing, and virulence factors of E. coli, such as adhesion, invasion, toxins, and iron acquisition. In total, 72 E. coli strains were identified in 71 cases, most of which primarily belonged to the B2 phylogroup (68.1%). The presence of the iutA gene (77.3% in the non-severe group, 46.4% in the severe group, P = 0.011) and the ibeA gene (9.1% in the non-severe group, and 35.7% in the severe group, P = 0.012) was significantly associated with the severity of infection. Among the patient characteristics, diabetes mellitus with organ involvement and alkaline phosphatase were different in the severe and non-severe groups. Conclusions We showed that bacteremic E. coli strains from acute biliary tract infections belonged to the virulent (B2) phylogroup. The prevalence of the iutA and ibeA genes between the two groups of bacteremia severity was significantly different.


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