Blood eosinophils during bronchiolitis: Associations with atopy, asthma and lung function in young adults.

AIM: To study if blood eosinophils during bronchiolitis were associated with atopy, asthma and lung function in young adults and if these associations differed between respiratory syncytial virus (RSV) bronchiolitis and non-RSV bronchiolitis. METHODS: This historical cohort enrolled 225 subjects. Blood eosinophils were measured during bronchiolitis in infancy, and the subjects were invited to a follow-up at 17-20 years of age including questionnaires for asthma and examinations of lung function and atopy. RESULTS: The level of eosinophils was positively associated with subsequent atopy in the unadjusted analysis, but not in the adjusted analysis, and not with asthma. There was a negative association between the level of eosinophils and forced vital capacity (FVC) (-0.11; -0.19, -0.02) and forced expiratory volume in first second (FEV1 ) (-0.12; -0.21, -0.03) (regression coefficient; 95% confidence interval). The non-RSV group had higher levels of eosinophils during bronchiolitis, but there was no interaction between the level of eosinophils and RSV status for any outcome. CONCLUSIONS: The level of eosinophils during bronchiolitis was negatively associated with lung function in young adult age, but we found no associations with atopy or asthma. These associations were not different after RSV bronchiolitis compared to non-RSV bronchiolitis.

Lung function and bronchial hyper-reactivity from 11 to 18 years in children with bronchiolitis in infancy.

BACKGROUND: Various trajectories for lung function and bronchial hyper-reactivity (BHR) from early childhood to adulthood are described, including puberty as a period with excessive lung growth. Bronchiolitis in infancy may be associated with increased risk of developing chronic obstructive pulmonary disease, but the development of respiratory patterns during puberty is poorly characterized for these children. We aimed to study the development and trajectories of lung function and BHR from 11 to 18 years of age in children hospitalized for bronchiolitis in infancy. METHODS: Infants hospitalized for bronchiolitis at the University Hospitals in Stavanger and Bergen, Norway, during 1997-1998, and an age-matched control group, were included in a longitudinal follow-up study and examined at 11 and 18 years of age with spirometry and methacholine provocation test (MPT). The MPT data were managed as dose-response slope (DRS) in the statistical analyses. Changes in lung function and DRS from 11 to 18 years of age were analyzed by generalized estimating equations, including interaction terms. RESULTS: z-scores for forced vital capacity (FVC), forced expiratory volume in first second (FEV1 ), FEV1 /FVC ratio, and DRS were not different from 11 to 18 years of age in both the post-bronchiolitis and the control group. The trajectories from 11 to 18 years did not differ between the two groups. BHR at age 11 was independently associated with asthma at age 18. CONCLUSION: Children hospitalized for bronchiolitis had stable predicted lung function and BHR from 11 to 18 years of age. The lung function trajectories were not different from controls.

Half of children with recurrent or chronic wet cough before three years of age were symptom-free by age seven.

AIM: We aimed to study the natural course of recurrent episodic and chronic wet cough in preschool children, the proportion and age of resolution, and risk factors for persistent symptoms. METHODS: Parents of children with recurrent or chronic wet cough who had attended the outpatient clinic before the age of three years during 2010-2013 at Stavanger University Hospital, Norway, answered a questionnaire regarding clinical symptoms and current medication at a follow-up in 2017-2018. RESULTS: We invited 840 children to participate, and parents consented for 348 (41.4%) of the children. At the first outpatient visit, 171 children (58.8%) had recurrent episodic and 120 (41.2%) had chronic wet cough. At follow-up at a median age of 82 months, 57.0% in both groups were symptom-free, and 9.4% with episodic cough and 13.3% with chronic cough had more than mild symptoms. During the last 12 months prior to the survey, 27.2% with episodic cough and 18.6% with chronic cough had used inhaled corticosteroids. CONCLUSION: Half of the preschool children with recurrent episodic or chronic wet cough outgrew their symptoms by the median age of seven years, but one in four still used inhaled corticosteroids.

[Proposal on the principles that should guide the ethical responsibilities of the state during the COVID-19 pandemic]. / Ética de la Salud Pública: propuesta sobre los principios fundamentales que guían las responsabilidades éticas del estado en el contexto pandemia COVID-19.

On March 11, 2020, the World Health Organization (WHO) stated that the number of cases of COVID-19 multiplied by 13 outside China, with a threefold increase in the number of affected countries. The WHO expressed its concern about the alarming levels of spread and severity of the outbreak, declaring the pandemic. This pandemic context is generating a social pact that seeks to ensure collective protection over individual freedoms. To meet the challenge, Governments must make decisions based on the principles that govern the State- These should consider the differences and particularities of those affected, without diverting attention from collective social protection. The following is a proposal on the ethical principles that should guide a State that makes decisions in public health emergencies.

[Primary Care Assessment Tool applied to primary health care workers from Conchalí, Santiago]. / Estructura y funciones de la Atención Primaria de Salud según el Primary Care Assessment Tool para prestadores en la comuna de Conchalí - Santiago de Chile.

BACKGROUND: The Chilean public health system is based on Primary Health Care (PHC), whose assessment is challenging due to the heterogeneity of services and multi-dimensionality of expected results. The Primary Care Assessment Tool was adapted and validated for Chile. AIM: To analyze, from the provider's perspective, the structure and functioning of the health centers, to determine the achievement of PHC's core functions: access, continuity, coordination, comprehensiveness of care, cultural competence, family centeredness and community orientation. MATERIAL AND METHODS: All professionals working in primary care in a commune of Metropolitan Santiago were invited to answer an online version of the Primary Care Assessment Tool. RESULTS: One hundred and nine professionals (51% of those invited) from four Family Health Centers, two Community Health Centers, and a Community Mental Health Center, answered the online questionnaire. Their distribution by profession and health units does not resemble the whole research population, which should be considered when interpreting the results. Data show a good performance of the system: general and domain specific scores are all near three for a maximum score of four. Family centeredness obtained the highest score, whereas cultural competence had the lowest. CONCLUSIONS: Reinforcing intercultural skills and a wider approach to psycho-social problems is recommended to strengthen the new healthcare model implementation.

Dose- and time-dependent effects of triethylene glycol dimethacrylate on the proteome of human THP-1 monocytes.

Triethylene glycol dimethacrylate (TEGDMA) is commonly used in polymer resin-based dental materials. This study investigated the molecular mechanisms of TEGDMA toxicity by identifying its time- and dose-dependent effects on the proteome of human THP-1 monocytes. The effects of different concentrations (0.07-5 mM) and exposure times (0-72 h) of TEGDMA on cell viability, proliferation, and morphology were determined using a real-time viability assay, automated cell counting, and electron microscopy, and laid the fundament for choice of exposure scenarios in the proteomic experiments. Solvents were not used, as TEGDMA is soluble in cell culture medium (determined by photon correlation spectroscopy). Cells were metabolically labeled [using the stable isotope labeled amino acids in cell culture (SILAC) strategy], and exposed to 0, 0.3 or 2.5 mM TEGDMA for 6 or 16 h before liquid chromatography-tandem mass spectrometry (LC-MS/MS) analyses. Regulated proteins were analyzed in the STRING database. Cells exposed to 0.3 mM TEGDMA showed increased viability and time-dependent upregulation of proteins associated with stress/oxidative stress, autophagy, and cytoprotective functions. Cells exposed to 2.5 mM TEGDMA showed diminished viability and a protein expression profile associated with oxidative stress, DNA damage, mitochondrial dysfunction, and cell cycle inhibition. Altered expression of immune genes was observed in both groups. The study provides novel knowledge about TEGDMA toxicity at the proteomic level. Of note, even low doses of TEGDMA induced a substantial cellular response.

Librarians Flip for Students: Teaching Searching Skills to Medical Students Using a Flipped Classroom Approach.

This article describes the development of a flipped classroom instructional module designed by librarians to teach first- and second-year medical students how to search the literature and find evidence-based articles. The pre-class module consists of an online component that includes reading, videos, and exercises relating to a clinical case. The in-class sessions, designed to reinforce important concepts, include various interactive activities. The specifics of designing both components are included for other health sciences librarians interested in presenting similar instruction. Challenges encountered, particularly in the live sessions, are detailed, as are the results of evaluations submitted by the students, who largely enjoyed the online component. Future plans are contingent on solving technical problems encountered during the in-class sessions.

Upregulation of Mrps18a in breast cancer identified by selecting phage antibody libraries on breast tissue sections.

BACKGROUND: One of the hallmarks of cancer is an altered energy metabolism, and here, mitochondria play a central role. Previous studies have indicated that some mitochondrial ribosomal proteins change their expression patterns upon transformation. METHOD: In this study, we have used the selection of recombinant antibody libraries displayed on the surface of filamentous bacteriophage as a proteomics discovery tool for the identification of breast cancer biomarkers. A small subpopulation of breast cells expressing both cytokeratin 19 and cytokeratin 14 was targeted using a novel selection procedure. RESULTS: We identified the mitochondrial ribosomal protein s18a (Mrps18a) as a protein which is upregulated in breast cancer. However, Mrps18a was not homogeneously upregulated in all cancer cells, suggesting the existence of sub-populations within the tumor. The upregulation was not confined to cytokeratin 19 and cytokeratin 14 double positive cells. CONCLUSION: This study illustrates how phage display can be applied towards the discovery of proteins which exhibit changes in their expression patterns. We identified the mitochondrial protein Mrps18a as being upregulated in human breast cancer cells compared to normal breast cells.

A novel variant in MYLK causes thoracic aortic dissections: genotypic and phenotypic description.

BACKGROUND: Mutations in MYLK cause non-syndromic familial thoracic aortic aneurysms and dissections (FTAAD). Very little is known about the phenotype of affected families. We sought to characterize the aortic disease and the presence of other vascular abnormalities in FTAAD caused by a deletion in MYLK and to compare thoracic aortic diameter and stiffness in mutation carriers and non-carriers. METHODS: We studied FTAAD in a 5-generation family that included 19 living members. Exome sequencing was performed to identify the underlying gene defect. Aortic elastic properties measured by TTE, MRI and pulse wave velocity were then compared between mutation carriers and non-carriers. RESULTS: Exome sequencing led to the identification of a 2-bp deletion in MYLK (c3272_3273del, p.Ser1091*) that led to a premature stop codon and nonsense-mediated decay. Eleven people were mutation carriers and eight people were non-carriers. Five aortic ruptures or dissections occurred in this family, with two survivors. There were no differences in aortic diameter or stiffness between carriers and non-carriers of the mutation. CONCLUSIONS: Individuals carrying this deletion in MYLK have a high risk of presenting with an acute aortic dissection or rupture. Aortic events occur over a wide range of ages and are not always preceded by obvious aortic dilatation. Aortic elastic properties do not differ between carriers and non-carriers of this mutation, rendering it uncertain whether and when carriers should undergo elective prophylactic surgery.

The zinc transporter ZNT3 co-localizes with insulin in INS-1E pancreatic beta cells and influences cell survival, insulin secretion capacity, and ZNT8 expression.

Zinc trafficking in pancreatic beta cells is tightly regulated by zinc transporting (ZNTs) proteins. The role of different ZNTs in the beta cells is currently being clarified. ZNT8 transports zinc into insulin granules and is critical for a correct insulin crystallization and storage in the granules whereas ZNT3 knockout negatively affects beta cell function and survival. Here, we describe for the first time the sub-cellular localization of ZNT3 by immuno-gold electron microscopy and supplement previous data from knockout experiments with investigations of the effect of ZNT3 in a pancreatic beta cell line, INS-1E overexpressing ZNT3. In INS-1E cells, we found that ZNT3 was abundant in insulin containing granules located close to the plasma membrane. The level of ZNT8 mRNA was significantly decreased upon over-expression of ZNT3 at different glucose concentrations (5, 11 and 21 mM glucose). ZNT3 over-expression decreased insulin content and insulin secretion whereas ZNT3 over-expression improved the cell survival after 24 h at varying glucose concentrations (5, 11 and 21 mM). Our data suggest that ZNT3 and ZNT8 (known to regulate insulin secretion) have opposite effects on insulin synthesis and secretion possibly by a transcriptional co-regulation since mRNA expression of ZNT3 was inversely correlated to ZNT8 and ZNT3 over-expression reduced insulin synthesis and secretion in INS-1E cells. ZNT3 over-expression improved cell survival.

Methods and terminology used in cell-culture studies of low-dose effects of matrix constituents of polymer resin-based dental materials.

General comprehension of terms and confounding factors associated with in vitro experiments can maximize the potential of in vitro testing of substances. In this systematic review, we present an overview of the terms and methods used to determine low-dose effects of matrix constituents in polymer resin-based dental materials in cell-culture studies and discuss the findings in light of how they may influence the comprehension and interpretation of results. Articles published between 1996 and 2015 were identified by searches in the Scopus, Web of Science, MEDLINE, PubMed, and Embase databases using keywords associated with low-dose effects, polymer resin-based materials, in vitro parameters, and dental materials. Twenty-nine articles were included. Subtoxic (n = 11), sublethal (n = 10), and nontoxic (n = 6) were the terms most commonly used to describe the low-dose effects of methacrylates. However, definition of terms varied. Most (82%) studies employed only one method to define the exposure scenario, and no agreement was seen between studies on the use of solvents. Prophylactic use of antibiotics was widespread, and mycoplasma screening was not reported. In conclusion, cell-culture conditions and tests used to define exposure scenarios have changed little in the last decades, despite development in recommendations. Nomenclature alignment is needed for a better understanding of possible biohazards of methacrylates.

Imaging fenestrations in liver sinusoidal endothelial cells by optical localization microscopy.

Liver sinusoidal endothelial cells (LSEC) are an important class of endothelial cells facilitating the translocation of lipoproteins and small molecules between the liver and blood. A number of clinical conditions, especially metabolic and aging-related disorders, are implicated by improper function of LSECs. Despite their importance, research into these cells is limited because the primary ultrastructures involved in their function are transcellular pores, called fenestrations, with diameters in a size range between 50-200 nm, i.e. well below the optical diffraction limit. Here, we show that we are able to resolve fenestrations with a spatial resolution of ∼20 nm by direct stochastic optical reconstruction microscopy (dSTORM). The cellular plasma membrane was labeled at high fluorophore density with CellMask Deep Red and imaged using a reducing buffer system. We compare the higher degree of structural detail that dSTORM provides to results obtained by 3D structured illumination microscopy (3D-SIM). Our results open up a path to image these physiologically important cells in vitro using highly resolving localization microscopy techniques that could be implemented on non-specialized fluorescence microscopes, enabling their investigation in most biomedical laboratories without the need for electron microscopy.

Liver sinusoidal cells eliminate blood-borne phage K1F.

Phage treatment has regained attention due to an increase in multiresistant bacteria. For phage therapy to be successful, phages must reach their target bacteria in sufficiently high numbers. Blood-borne phages are believed to be captured by macrophages in the liver and spleen. Since liver sinusoids also consist of specialized scavenger liver sinusoidal endothelial cells (LSECs) and Kupffer cells (KCs), this study investigated the contribution of both cell types in the elimination of Escherichia coli phage K1Fg10b::gfp (K1Fgfp) in mice. Circulatory half-life, organ, and hepatocellular distribution of K1Fgfp were determined following intravenous administration. Internalization of K1Fgfp and effects of phage opsonization on uptake were explored using primary mouse and human LSEC and KC cultures. When inoculated with 107 virions, >95% of the total K1Fgfp load was eliminated from the blood within 20 min, and 94% of the total retrieved K1Fgfp was localized to the liver. Higher doses resulted in slower elimination, possibly reflecting temporary saturation of liver scavenging capacity. Phage DNA was detected in both cell types, with a KC:LSEC ratio of 12:1 per population following cell isolation. Opsonization with plasma proteins increased time-dependent cellular uptake in both LSECs and KCs in vitro. Internalized phages were rapidly transported along the endocytic pathway to lysosomal compartments. Reduced viability of intracellular K1Fgfp corroborated inactivation following endocytosis. This study is the first to identify phage distribution in the liver at the hepatocellular level, confirming clearance of K1Fgfp performed mostly by KCs with a significant uptake also in LSECs.IMPORTANCEFaced with the increasing amounts of bacteria with multidrug antimicrobial resistance, phage therapy has regained attention as a possible treatment option. The phage field has recently experienced an emergence in commercial interest as research has identified new and more efficient ways of identifying and matching phages against resistant superbugs. Currently, phages are unapproved drugs in most parts of the world. For phages to reach broad clinical use, they must be shown to be clinically safe and useful. The results presented herein contribute to increased knowledge about the pharmacokinetics of the T7-like phage K1F in the mammalian system. The cell types of the liver that are responsible for rapid phage blood clearance are identified. Our results highlight the need for more research about appropriate dose regimens when phage therapy is delivered intravenously and advise essential knowledge about cell systems that should be investigated further for detailed phage pharmacodynamics.

Cardiopulmonary involvement in Puumala hantavirus infection.

BACKGROUND: Hantavirus infections cause potentially life-threatening disease in humans world-wide. Infections with American hantaviruses may lead to hantavirus pulmonary syndrome characterised by severe cardiopulmonary distress with high mortality. Pulmonary involvement in European Puumala hantavirus (PUUV) infection has been reported, whereas knowledge of potential cardiac manifestations is limited. We aimed to comprehensively investigate cardiopulmonary involvement in patients with PUUV-infection. METHODS: Twenty-seven hospitalised patients with PUUV-infection were examined with lung function tests, chest high-resolution CT (HRCT), echocardiography including speckle tracking strain rate analysis, ECG and measurements of cardiac biomarkers N-terminal pro-B-type natriuretic peptide (NT-ProBNP) and troponin T. Patients were re-evaluated after 3 months. Twenty-five age and sex-matched volunteers acted as controls for echocardiography data. RESULTS: Two-thirds of the patients experienced respiratory symptoms as dry cough or dyspnoea. Gas diffusing capacity was impaired in most patients, significantly improving at follow-up but still subnormal in 38%. HRCT showed thoracic effusions or pulmonary oedema in 46% of the patients. Compared to controls, the main echocardiographic findings in patients during the acute phase were significantly higher pulmonary vascular resistance, higher systolic pulmonary artery pressure, lower left ventricular ejection fraction and impaired left atrial myocardial motion. Pathological ECG, atrial fibrillation or T-wave changes, was demonstrated in 26% of patients. NT-ProBNP concentrations were markedly increased and were inversely associated with gas diffusing capacity but positively correlated to pulmonary vascular resistance. Furthermore, patients experiencing impaired general condition at follow-up had significantly lower gas diffusing capacity and higher pulmonary vascular resistance, compared to those feeling fully recovered. CONCLUSIONS: In a majority of patients with PUUV-infection, both cardiac and pulmonary involvement was demonstrated with implications on patients' recovery. The results demonstrate vascular leakage in the lungs that most likely is responsible for impaired gas diffusing capacity and increased pulmonary vascular resistance with secondary pulmonary hypertension and right heart distress. Interestingly, NT-ProBNP was markedly elevated even in the absence of overt ventricular heart failure. The method of simultaneous investigations of important cardiac and respiratory measurements improves the interpretation of the underlying pathophysiologic mechanisms.

Infection of liver sinusoidal endothelial cells with Muromegalovirus muridbeta1 involves binding to neuropilin-1 and is dynamin-dependent.

Liver sinusoidal endothelial cells (LSEC) are scavenger cells with a remarkably high capacity for clearance of several blood-borne macromolecules and nanoparticles, including some viruses. Endocytosis in LSEC is mainly via the clathrin-coated pit mediated route, which is dynamin-dependent. LSEC can also be a site of infection and latency of betaherpesvirus, but mode of virus entry into these cells has not yet been described. In this study we have investigated the role of dynamin in the early stage of muromegalovirus muridbeta1 (MuHV-1, murid betaherpesvirus 1, murine cytomegalovirus) infection in mouse LSECs. LSEC cultures were freshly prepared from C57Bl/6JRj mouse liver. We first examined dose- and time-dependent effects of two dynamin-inhibitors, dynasore and MitMAB, on cell viability, morphology, and endocytosis of model ligands via different LSEC scavenger receptors to establish a protocol for dynamin-inhibition studies in these primary cells. LSECs were challenged with MuHV-1 (MOI 0.2) ± dynamin inhibitors for 1h, then without inhibitors and virus for 11h, and nuclear expression of MuHV-1 immediate early antigen (IE1) measured by immune fluorescence. MuHV-1 efficiently infected LSECs in vitro. Infection was significantly and independently inhibited by dynasore and MitMAB, which block dynamin function via different mechanisms, suggesting that initial steps of MuHV-1 infection is dynamin-dependent in LSECs. Infection was also reduced in the presence of monensin which inhibits acidification of endosomes. Furthermore, competitive binding studies with a neuropilin-1 antibody blocked LSEC infection. This suggests that MuHV-1 infection in mouse LSECs involves virus binding to neuropilin-1 and occurs via endocytosis.

Are BMI and adipokines associated with asthma, atopy and lung function in young adults previously hospitalized for bronchiolitis?

BACKGROUND: Children hospitalized for bronchiolitis have increased risk of asthma and low lung function persisting into adulthood, but the underlying mechanisms are poorly understood. Body mass index (BMI) and adipokines are associated with respiratory morbidity. We aimed to investigate if associations between BMI and adipokines and the outcomes asthma, atopy, and lung function differed between young adults previously hospitalized for bronchiolitis and control subjects. METHODS: This sub study of a historical cohort enrolled 185 young adults previously hospitalized for bronchiolitis and 146 matched control subjects. Exposures (BMI and the adipokines: adiponectin, leptin, resistin, and ghrelin) and outcomes (asthma, atopy, and lung function) were measured cross-sectionally at 17-20 years of age. Associations were tested in regression models, and differences between the post-bronchiolitis- and control group were tested by including interaction terms. RESULTS: BMI was associated with asthma and lung function, but we did not find that the associations differed between the post-bronchiolitis- and control group. We also found some associations between adipokines and outcomes, but only associations between adiponectin and forced vital capacity (FVC) and between resistin and current asthma differed between the groups (p-value interaction term 0.027 and 0.040 respectively). Adiponectin tended to be positively associated with FVC in the post-bronchiolitis group, with an opposite tendency in the control group. Resistin was positively associated with current asthma only in the control group. CONCLUSION: The increased prevalence of asthma and impaired lung function observed in young adults previously hospitalized for bronchiolitis do not seem to be related to growth and fat metabolism.

Decellularization of the Human Liver to Generate Native Extracellular Matrix for Use in Automated Functional Assays with Stellate Cells.

With the incidence of liver disease on the rise globally, increasing numbers of patients are presenting with advanced hepatic fibrosis and significant mortality risk. The demand far outstrips possible transplantation capacities, and thus there is an intense drive to develop new pharmacological therapies that stall or reverse liver scarring. Recent late-stage failures of lead compounds have highlighted the challenges of resolving fibrosis, which has developed and stabilized over many years and varies in nature and composition from individual to individual. Hence, preclinical tools are being developed in both the hepatology and tissue engineering communities to elucidate the nature, composition, and cellular interactions of the hepatic extracellular niche in health and disease. In this protocol, we describe strategies for decellularizing cirrhotic and healthy human liver specimens and show how these can be used in simple functional assays to detect the impact on stellate cell function. Our simple, small-scale approach is translatable to diverse lab settings and generates cell-free materials which could be used for a variety of in vitro analyses as well as a scaffold for repopulating with key hepatic cell populations.

Liver sinusoidal endothelial cells show reduced scavenger function and downregulation of Fc gamma receptor IIb, yet maintain a preserved fenestration in the Glmpgt/gt mouse model of slowly progressing liver fibrosis.

Liver sinusoidal endothelial cells (LSECs) are fenestrated endothelial cells with a unique, high endocytic clearance capacity for blood-borne waste macromolecules and colloids. This LSEC scavenger function has been insufficiently characterized in liver disease. The Glmpgt/gt mouse lacks expression of a subunit of the MFSD1/GLMP lysosomal membrane protein transporter complex, is born normal, but soon develops chronic, mild hepatocyte injury, leading to slowly progressing periportal liver fibrosis, and splenomegaly. This study examined how LSEC scavenger function and morphology are affected in the Glmpgt/gt model. FITC-labelled formaldehyde-treated serum albumin (FITC-FSA), a model ligand for LSEC scavenger receptors was administered intravenously into Glmpgt/gt mice, aged 4 months (peak of liver inflammation), 9-10 month, and age-matched Glmpwt/wt mice. Organs were harvested for light and electron microscopy, quantitative image analysis of ligand uptake, collagen accumulation, LSEC ultrastructure, and endocytosis receptor expression (also examined by qPCR and western blot). In both age groups, the Glmpgt/gt mice showed multifocal liver injury and fibrosis. The uptake of FITC-FSA in LSECs was significantly reduced in Glmpgt/gt compared to wild-type mice. Expression of LSEC receptors stabilin-1 (Stab1), and mannose receptor (Mcr1) was almost similar in liver of Glmpgt/gt mice and age-matched controls. At the same time, immunostaining revealed differences in the stabilin-1 expression pattern in sinusoids and accumulation of stabilin-1-positive macrophages in Glmpgt/gt liver. FcγRIIb (Fcgr2b), which mediates LSEC endocytosis of soluble immune complexes was widely and significantly downregulated in Glmpgt/gt liver. Despite increased collagen in space of Disse, LSECs of Glmpgt/gt mice showed well-preserved fenestrae organized in sieve plates but the frequency of holes >400 nm in diameter was increased, especially in areas with hepatocyte damage. In both genotypes, FITC-FSA also distributed to endothelial cells of spleen and bone marrow sinusoids, suggesting that these locations may function as possible compensatory sites of clearance of blood-borne scavenger receptor ligands in liver fibrosis.