CD14 expression and Kupffer cell dysfunction in non‐alcoholic steatohepatitis: Superparamagnetic iron oxide‐magnetic resonance image and pathologic correlation

Tonan, Tatsuyuki; Fujimoto, Kiminori; Qayyum, Aliya; Morita, Yasuyo; Nakashima, Osamu; Ono, Noriyuki; Kawahara, Akihiko; Kage, Masayoshi; Hayabuchi, Naofumi; Ueno, Takato

doi:10.1111/j.1440-1746.2011.07057.x

Cited by 27 publications

(30 citation statements)

References 35 publications

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“…has shown that inheritance of the 2518 MCP-1 G allele predisposes patients infected with the hepatitis C virus to more severe hepatic inflammation and fibrosis. Finally, Tonan et al 62. reported that Kupffer cell dysfunction contributes to the pathogenesis of non-alcoholic steatohepatitis, as CD14-positive Kupffer cells increase along with increase in necroinflammation grade and fibrosis stage.…”

Section: Immunological Dysfunction In Cirrhosismentioning

confidence: 99%

Immune Dysfunction in Cirrhosis

Noor¹,

Manoria²

2017

Journal of Clinical and Translational Hepatology

117

105

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Cirrhosis due to any etiology disrupts the homeostatic role of liver in the body. Cirrhosis-associated immune dysfunction leads to alterations in both innate and acquired immunity, due to defects in the local immunity of liver as well as in systemic immunity. Cirrhosis-associated immune dysfunction is a dynamic phenomenon, comprised of both increased systemic inflammation and immunodeficiency, and is responsible for 30% mortality. It also plays an important role in acute as well as chronic decompensation. Immune paralysis can accompany it, which is characterized by increase in antiinflammatory cytokines and suppression of proinflammatory cytokines. There is also presence of increased gut permeability, reduced gut motility and altered gut flora, all of which leads to increased bacterial translocation. This increased bacterial translocation and consequent endotoxemia leads to increased blood stream bacterial infections that cause systemic inflammatory response syndrome, sepsis, multiorgan failure and death. The gut microbiota of cirrhotic patients has more pathogenic microbes than that of noncirrhotic individuals, and this disturbs the homeostasis and favors gut translocation. Prompt diagnosis and treatment of such infections are necessary for better survival. We have reviewed the various mechanisms of immune dysfunction and its consequences in cirrhosis. Recognizing the exact pathophysiology of immune dysfunction will help treating clinicians in avoiding its complications in their patients and can lead to newer therapeutic interventions and reducing the morbidity and mortality rates. Citation of this article: Noor MT, Manoria P. Immune dysfunction in cirrhosis.

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Section: Immunological Dysfunction In Cirrhosismentioning

confidence: 99%

Immune Dysfunction in Cirrhosis

Noor¹,

Manoria²

2017

Journal of Clinical and Translational Hepatology

117

105

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“…17 In contrast to USPIO, SPIONs are characterized by enhanced liver accumulation, thereby constituting a superb hepatic MRI contrast agent. Low concentrations of SPIONs (0.5 mg Fe/kg of carboxydextran-coated ferucarbotran (Resovist/Ferrixan, 45-60 nm [18][19][20], or dextran-coated ferumoxides (Endorem/Feridex), 21 have been used to noninvasively distinguish between benign liver condition (simple steatosis) and nonalcoholic steatohepatitis (NASH), which is highly associated with cardiovascular and renal comorbidities. 22 Despite promising results in humans, the marketing of intravenous iron oxide-containing contrast agents is currently at a standstill.…”

Section: Introductionmentioning

confidence: 99%

Non-immunogenic dextran-coated superparamagnetic iron oxide nanoparticles: a biocompatible, size-tunable contrast agent for magnetic resonance imaging

Unterweger

Janko

Schwarz

et al. 2017

IJN

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Iron oxide-based contrast agents have been in clinical use for magnetic resonance imaging (MRI) of lymph nodes, liver, intestines, and the cardiovascular system. Superparamagnetic iron oxide nanoparticles (SPIONs) have high potential as a contrast agent for MRI, but no intravenous iron oxide-containing agents are currently approved for clinical imaging. The aim of our work was to analyze the hemocompatibility and immuno-safety of a new type of dextran-coated SPIONs (SPIONdex) and to characterize these nanoparticles with ultra-high-field MRI. Key parameters related to nanoparticle hemocompatibility and immuno-safety were investigated in vitro and ex vivo. To address concerns associated with hypersensitivity reactions to injectable nanoparticulate agents, we analyzed complement activation-related pseudoallergy (CARPA) upon intravenous administration of SPIONdex in a pig model. Furthermore, the size-tunability of SPIONdex and the effects of size reduction on their biocompatibility were investigated. In vitro, SPIONdex did not induce hemolysis, complement or platelet activation, plasma coagulation, or leukocyte procoagulant activity, and had no relevant effect on endothelial cell viability or endothelial–monocytic cell interactions. Furthermore, SPIONdex did not induce CARPA even upon intravenous administration of 5 mg Fe/kg in pigs. Upon SPIONdex administration in mice, decreased liver signal intensity was observed after 15 minutes and was still detectable 24 h later. In addition, by changing synthesis parameters, a reduction in particle size <30 nm was achieved, without affecting their hemo- and biocompatibility. Our findings suggest that due to their excellent biocompatibility, safety upon intravenous administration and size-tunability, SPIONdex particles may represent a suitable candidate for a new-generation MRI contrast agent.

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“…5B and C. The peak enhancement in T 2 -weighted MRI of normal liver parenchyma could be obtained at 30 min post the injection of Fe 3 O 4 -Au NPs, which was significantly later than that of the normal rats. We speculated that the time delay to the phagocytosis dysfunction was caused by liver cirrhosis [54]. On this basis, a much faster washout of Fe 3 O 4 -Au NPs could be observed with respect to that of normal rats (washout rate represented with MR signal intensity reduction estimated with R2 48h /R2 30min, ca.…”

Section: Mr and Ct Measurements In Cirrhotic Livermentioning

confidence: 97%

Synthesis and application of strawberry-like Fe 3 O 4 -Au nanoparticles as CT-MR dual-modality contrast agents in accurate detection of the progressive liver disease

Zhao

Liu

et al. 2015

Biomaterials

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CD14 expression and Kupffer cell dysfunction in non‐alcoholic steatohepatitis: Superparamagnetic iron oxide‐magnetic resonance image and pathologic correlation

Abstract: KC phagocytic function evaluated with SPIO-MRI correlated with histopathological severity and number of CD14-positive KCs. These results support the concept that KC phagocytic dysfunction contributes to the pathogenesis of NASH.

Cited by 27 publications

References 35 publications

Immune Dysfunction in Cirrhosis

Immune Dysfunction in Cirrhosis

Non-immunogenic dextran-coated superparamagnetic iron oxide nanoparticles: a biocompatible, size-tunable contrast agent for magnetic resonance imaging

Synthesis and application of strawberry-like Fe 3 O 4 -Au nanoparticles as CT-MR dual-modality contrast agents in accurate detection of the progressive liver disease

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