scholarly journals Hofbauer cells and coronavirus disease 2019 (COVID-19) in pregnancy: Molecular pathology analysis of villous macrophages, endothelial cells, and placental findings from 22 placentas infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with and without fetal transmission

2021 ◽  
Author(s):  
David A. Schwartz ◽  
Marcella Baldewijns ◽  
Alexandra Benachi ◽  
Mattia Bugatti ◽  
Gaetano Bulfamante ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Severe Acute Respiratory Syndrome ◽  
Molecular Pathology ◽  
Capillary Endothelium ◽  
Cell Hyperplasia ◽  
Cell Staining ◽  
Hofbauer Cells ◽  
Capillary Endothelial Cells ◽  
Placental Macrophages ◽  
Maternal Fetal Transmission

Context.– Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can undergo maternal-fetal transmission, heightening interest in the placental pathology findings from this infection. Transplacental SARS-CoV-2 transmission is typically accompanied by chronic histiocytic intervillositis together with necrosis and positivity of syncytiotrophoblast for SARSCoV-2. Hofbauer cells are placental macrophages that have been involved in viral diseases including HIV and Zika virus, but their involvement in SARS-CoV-2 in unknown. Objective.– To determine whether SARS-CoV-2 can extend beyond the syncytiotrophoblast to enter Hofbauer cells, endothelium and other villous stromal cells in infected placentas of liveborn and stillborn infants. Design.– Case-based retrospective analysis by 29 perinatal and molecular pathology specialists of placental findings from a preselected cohort of 22 SARS-CoV-2-infected placentas delivered to pregnant women testing positive for SARS-CoV-2 from 7 countries. Molecular pathology methods were used to investigate viral involvement of Hofbauer cells, villous capillary endothelium, syncytiotrophoblast and other fetal-derived cells. Results.– Chronic histiocytic intervillositis and trophoblast necrosis was present in all 22 placentas (100%). SARS-CoV-2 was identified in Hofbauer cells from 4/22 placentas (18%). Villous capillary endothelial staining was positive in 2/22 cases (9%), both of which also had viral positivity in Hofbauer cells. Syncytiotrophoblast staining occurred in 21/22 placentas (95%). Hofbauer cell hyperplasia was present in 3/22 placentas (14%). In the 7 cases having documented transplacental infection of the fetus, 2 occurred in placentas with Hofbauer cell staining positive for SARS-CoV-2. Conclusions.– SARS-CoV-2 can extend beyond the trophoblast into the villous stroma, involving Hofbauer cells and capillary endothelial cells, in a small number of infected placentas. Most cases of SARS-CoV-2 transplacental fetal infection occur without Hofbauer cell involvement.

scholarly journals Antibodies to mouse lung capillary endothelium.

1988 ◽  
Vol 36 (7) ◽  
pp. 741-749 ◽  
Author(s):  
M C Rorvik ◽  
D P Allison ◽  
J A Hotchkiss ◽  
H P Witschi ◽  
S J Kennel
Keyword(s):  
Endothelial Cells ◽  
Cell Types ◽  
Interstitial Cells ◽  
Mouse Lung ◽  
Capillary Endothelium ◽  
Specific Cell ◽  
Alveolar Wall ◽  
Gold Particles ◽  
Capillary Endothelial Cells ◽  
Quantitative Analyses

We are interested in developing monoclonal antibodies (MoAbs) that recognize specific cell types in the lung of BALB/c mice. Normal mouse lung homogenate was used to immunize F344 rats and hybridomas were produced by fusion of rat spleen cells with mouse myeloma SP 2/0. Two hybridomas were selected which produced MoAbs active in immunohistochemistry of lung cells. MoAb 273-34A and 411-201B both show extensive peroxidase staining of capillary endothelial cells within alveolar walls of lungs at the light microscopic level. To demonstrate cell specificity, immunoelectron microscopy with gold-labeled antibody was performed. Lightly fixed lungs were frozen and thin-sectioned before staining with MoAb and 5-nm gold particles coupled to secondary antibody. Quantitative analyses of these cryosections show that both antibodies, used at optimal concentrations, are specific for binding to capillary endothelial cells. More than 95% of the gold particles are associated with capillary endothelial cells on the thin side of the alveolar wall. When capillaries adjoined thick septa containing interstitial cells, about two thirds of the gold particles were associated with endothelial cells and about one quarter with interstitial cells. These MoAbs should be useful in studying the role of endothelial cells in toxic lung injury.

scholarly journals Molecular Pathology Analysis of SARS-CoV-2 in Syncytiotrophoblast and Hofbauer Cells in Placenta from a Pregnant Woman and Fetus with COVID-19

Pathogens ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 479
Author(s):  
Denise Morotti ◽  
Massimiliano Cadamuro ◽  
Elena Rigoli ◽  
Aurelio Sonzogni ◽  
Andrea Gianatti ◽  
...  
Keyword(s):  
Molecular Pathology ◽  
Nucleocapsid Protein ◽  
Positive Staining ◽  
Transplacental Transmission ◽  
Placental Pathology ◽  
Macrophage Marker ◽  
Immunodeficiency Virus ◽  
Hofbauer Cells ◽  
Maternal Fetal Transmission

A small number of neonates delivered to women with SARS-CoV-2 infection have been found to become infected through intrauterine transplacental transmission. These cases are associated with a group of unusual placental pathology abnormalities that include chronic histiocytic intervillositis, syncytiotrophoblast necrosis, and positivity of the syncytiotrophoblast for SARS-CoV-2 antigen or RNA. Hofbauer cells constitute a heterogeneous group of immunologically active macrophages that have been involved in transplacental infections that include such viral agents as Zika virus and human immunodeficiency virus. The role of Hofbauer cells in placental infection with SARS-CoV-2 and maternal-fetal transmission is unknown. This study uses molecular pathology techniques to evaluate the placenta from a neonate infected with SARS-CoV-2 via the transplacental route to determine whether Hofbauer cells have evidence of infection. We found that the placenta had chronic histiocytic intervillositis and syncytiotrophoblast necrosis, with the syncytiotrophoblast demonstrating intense positive staining for SARS-CoV-2. Immunohistochemistry using the macrophage marker CD163, SARS-CoV-2 nucleocapsid protein, and double staining for SARS-CoV-2 with RNAscope and anti-CD163 antibody, revealed that no demonstrable virus could be identified within Hofbauer cells, despite these cells closely approaching the basement membrane zone of the infected trophoblast. Unlike some other viruses, there was no evidence from this transmitting placenta for infection of Hofbauer cells with SARS-CoV-2.

scholarly journals SITES OF LIPOPROTEIN LIPASE ACTIVITY IN ADIPOSE TISSUE PERFUSED WITH CHYLOMICRONS

1971 ◽  
Vol 51 (1) ◽  
pp. 1-25 ◽  
Author(s):  
E. Joan Blanchette-Mackie ◽  
Robert O. Scow
Keyword(s):  
Endothelial Cells ◽  
Adipose Tissue ◽  
Lipoprotein Lipase ◽  
Lipase Activity ◽  
Capillary Endothelium ◽  
Lipoprotein Lipase Activity ◽  
Subendothelial Space ◽  
Capillary Endothelial Cells ◽  
E 600 ◽  
Cytochemical Reaction

Lipoprotein lipase activity was studied in rat parametrial adipose tissue perfused with chylomicrons and in gelatin blocks containing postheparin plasma and chylomicrons. The tissues and blocks were fixed in glutaraldehyde and incubated in 0.035 M CaCl2-0.1 M Tris medium (pH 8.3) at 38°C. The doubly labeled chylomicron triglycerides (glycerol-3H and palmitate-14C) in the tissues and blocks were hydrolyzed during incubation to free fatty acids (FFA) and the FFA remained in the specimens; hydrolysis was inhibited by 0.004 M diethyl paranitrophenyl phosphate (E-600). Incubated blocks and tissue were treated with 0.05 M Pb(NO3)2, postfixed in OsO4, dehydrated with acetone, embedded in Epon, and examined by electron microscopy. The incubated blocks contained electronlucent areas and granular and laminar precipitates at sites of hydrolysis. Similar precipitates were found in incubated tissue, within vacuoles and microvesicles of capillary endothelium, and in the subendothelial space (between the endothelium and pericytes), but not in the capillary lumen or in or near fat cells. The cytochemical reaction was greatly reduced, in blocks and tissues incubated with E-600. It is concluded that plasma glycerides are hydrolyzed by lipoprotein lipase in capillary endothelial cells and in the subendothelial space of adipose tissue and that glycerides across the endothelial cells within a membrane-bounded system.

Characterization of plasminogen binding to human capillary and arterial endothelial cells

1991 ◽  
Vol 69 (7) ◽  
pp. 442-448 ◽  
Author(s):  
Peter R. Ganz ◽  
Denis Dupuis ◽  
Anil K. Dudani ◽  
Sofia Hashemi
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Binding Sites ◽  
Phenotypic Diversity ◽  
Capillary Endothelium ◽  
Functional Differences ◽  
Equilibrium Binding ◽  
Capillary Endothelial Cells ◽  
Arterial Endothelial Cells

Phenotypic diversity of endothelial cells that line the various vascular spaces has been well established. However, it is not known if biochemical differences also exist, particularly in the numbers of receptors for plasma proteins. Equilibrium binding techniques were used to assess potential differences in the binding of 125I-labelled plasminogen to cultured human umbilical arterial endothelial cells and capillary endothelium, as compared with umbilical venous cells. The kinetic behaviour of plasminogen binding to all three types of cells was similar, with optimal binding occurring between 20 and 30 min of incubation. Binding of plasminogen to arterial, capillary, and venous cells was concentration dependent and reversible upon addition to excess unlabelled plasminogen. Scatchard analyses showed that artery, capillary, and venous endothelial cells all possess low affinity sites for plasminogen with Kd values of 0.30 ± 0.07, 0.40 ± 0.06, and 0.40 ± 0.08 μM, respectively. Vein cells also possess an additional higher affinity binding site with a Kd of 0.07 ± 0.01 μM, exhibiting a 6-fold greater affinity for plasminogen than the lower affinity sites on capillary and arterial endothelial cells. Assuming a stoichiometry of 1:1 for binding, the data indicate that arterial and capillary endothelial cells contain approximately 4.2 (± 0.9) × 106 and 4.1 (± 0.6) × 106 plasminogen receptors per cell. Venous cells contain both low and high density binding sites with 6.2 (± 0.8) × 106 and 12.4 (± 2.4) × 106 sites per endothelial cell. The presence of a higher affinity site on vein cells, but not on artery or capillary cells, may signal functional differences relating to fibrinolytic activity on the surface of these cells. Ligand blotting experiments, in which labelled plasminogen was adsorbed to polypeptides recovered from endothelial cell lysates, identified polypeptides of 46, 45, and 37 kDa, which may constitute the plasminogen-binding sites–receptors on endothelial cells.Key words: plasminogen, endothelial cells, receptors, fibrinolysis.

scholarly journals Molecular Pathology Demonstration of SARS-CoV-2 in Cytotrophoblast from Placental Tissue with Chronic Histiocytic Intervillositis, Trophoblast Necrosis and COVID-19

2021 ◽  
Vol 9 (3) ◽  
pp. 33
Author(s):  
David A. Schwartz ◽  
Mattia Bugatti ◽  
Amerigo Santoro ◽  
Fabio Facchetti
Keyword(s):  
Molecular Pathology ◽  
Placental Tissue ◽  
Physical Contact ◽  
Positive Staining ◽  
Fibrin Deposition ◽  
Cell Type ◽  
Hofbauer Cells ◽  
Capillary Endothelial Cells ◽  
Rna In Situ Hybridization ◽  
Cytotrophoblast Cells

A subset of placentas from pregnant women having the SARS-CoV-2 infection have been found to be infected with the coronavirus using molecular pathology methods including immunohistochemistry and RNA in situ hybridization. These infected placentas can demonstrate several unusual findings which occur together—chronic histiocytic intervillositis, trophoblast necrosis and positive staining of the syncytiotrophoblast for SARS-CoV-2. They frequently also have increased fibrin deposition, which can be massive in some cases. Syncytiotrophoblast is the most frequent fetal-derived cell type to be positive for SARS-CoV-2. It has recently been shown that in a small number of infected placentas, villous stromal macrophages, termed Hofbauer cells, and villous capillary endothelial cells can also stain positive for SARS-CoV-2. This report describes a placenta from a pregnant woman with SARS-CoV-2 that had chronic histiocytic intervillositis, trophoblast necrosis, increased fibrin deposition and positive staining of the syncytiotrophoblast for SARS-CoV-2. In addition, molecular pathology testing including RNAscope and immunohistochemistry for SARS-CoV-2 and double-staining immunohistochemistry using antibodies to E-cadherin and GATA3 revealed that cytotrophoblast cells stained intensely for SARS-CoV-2. All of the cytotrophoblast cells that demonstrated positive staining for SARS-CoV-2 were in direct physical contact with overlying syncytiotrophoblast that also stained positive for the virus. The pattern of cytotrophoblast staining for SARS-CoV-2 was patchy, and there were chorionic villi having diffuse positive staining of the syncytiotrophoblast for SARS-CoV-2, but without staining of cytotrophoblast. This first detailed description of cytotrophoblast involvement by SARS-CoV-2 adds another fetal cell type from infected placentas that demonstrate viral staining.

scholarly journals Diffuse cytoplasmic staining of retinal capillary endothelium.

1986 ◽  
Vol 34 (10) ◽  
pp. 1325-1330 ◽  
Author(s):  
W L Lin ◽  
E Essner
Keyword(s):  
Endothelial Cells ◽  
Capillary Endothelium ◽  
Electron Microscopic ◽  
Blood Retinal Barrier ◽  
Cytoplasmic Staining ◽  
Low Concentrations ◽  
Retinal Capillary ◽  
Capillary Endothelial Cells ◽  
Diffuse Cytoplasmic Staining ◽  
Electron Microscopic Cytochemistry

The distribution of several hemeprotein tracers in retinal capillaries of Wistar-Furth rats was studied by electron microscopic cytochemistry after incubation in 3,3'-diaminobenzidine. Diffuse cytoplasmic reaction product was frequently observed in the endothelial cells after intravenous injection of horseradish peroxidase (HRP) or lactoperoxidase (LP), or after perfusion of HRP. Occasionally, pericytes were also diffusely stained. In contrast, injection of microperoxidase, catalase, or hemoglobin did not cause diffuse staining. The diffuse staining was similar with HRP types II, VI, and VIII, and at concentrations of 2.5, 5, and 10 mg/100 g body weight. Despite the staining, the blood-retinal barrier remained intact. The findings indicate that HRP and LP are capable of causing diffuse nonspecific staining of retinal capillary endothelial cells, even at relatively low concentrations. Since these tracers are frequently used in studies of the blood-retinal barrier, the results of such studies should be interpreted with caution.

scholarly journals Age influences susceptibility of brain capillary endothelial cells to La Crosse virus infection and cell death

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Rahul Basu ◽  
Vinod Nair ◽  
Clayton W. Winkler ◽  
Tyson A. Woods ◽  
Iain D. C. Fraser ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Death ◽  
Virus Infection ◽  
La Crosse Virus ◽  
Brain Capillary ◽  
Adult Mice ◽  
Age Related ◽  
Capillary Endothelial Cells ◽  
The Brain

Abstract Background A key factor in the development of viral encephalitis is a virus crossing the blood-brain barrier (BBB). We have previously shown that age-related susceptibility of mice to the La Crosse virus (LACV), the leading cause of pediatric arbovirus encephalitis in the USA, was associated with the ability of the virus to cross the BBB. LACV infection in weanling mice (aged around 3 weeks) results in vascular leakage in the olfactory bulb/tract (OB/OT) region of the brain, which is not observed in adult mice aged > 6–8 weeks. Thus, we studied age-specific differences in the response of brain capillary endothelial cells (BCECs) to LACV infection. Methods To examine mechanisms of LACV-induced BBB breakdown and infection of the CNS, we analyzed BCECs directly isolated from weanling and adult mice as well as established a model where these cells were infected in vitro and cultured for a short period to determine susceptibility to virus infection and cell death. Additionally, we utilized correlative light electron microscopy (CLEM) to examine whether changes in cell morphology and function were also observed in BCECs in vivo. Results BCECs from weanling, but not adult mice, had detectable infection after several days in culture when taken ex vivo from infected mice suggesting that these cells could be infected in vitro. Further analysis of BCECs from uninfected mice, infected in vitro, showed that weanling BCECs were more susceptible to virus infection than adult BCECs, with higher levels of infected cells, released virus as well as cytopathic effects (CPE) and cell death. Although direct LACV infection is not detected in the weanling BCECs, CLEM analysis of brain tissue from weanling mice indicated that LACV infection induced significant cerebrovascular damage which allowed virus-sized particles to enter the brain parenchyma. Conclusions These findings indicate that BCECs isolated from adult and weanling mice have differential viral load, infectivity, and susceptibility to LACV. These age-related differences in susceptibility may strongly influence LACV-induced BBB leakage and neurovascular damage allowing virus invasion of the CNS and the development of neurological disease.

Interaction of Neutrophils with Endothelial Cells, Fibroblasts and Their Extracellular Matrices: Microscopic and Computerised Analysis

1988 ◽  
Vol 16 (1) ◽  
pp. 48-53
Author(s):  
Marina Ziche ◽  
Lucia Morbidelli ◽  
Annalisa Rubino ◽  
Piero Dolara ◽  
Stefano Bianchi ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Image Analysis ◽  
Vascular Endothelial Cells ◽  
Extracellular Matrices ◽  
Polymorphonuclear Neutrophil ◽  
Initial Event ◽  
Computerised Image Analysis ◽  
Capillary Endothelial Cells ◽  
Vitro Model

Polymorphonuclear neutrophil (PMN) interaction with vascular endothelial cells is the initial event in the migration of neutrophils through blood vessel walls before reaching inflammation sites in tissues. The interaction between fibroblasts and endothelial cells and their extracellular matrices might be modulated by the activation of neutrophils that occurs at inflammatory reaction sites. We have used an in vitro model to study PMN function, measuring the adhesion of human PMNs to capillary endothelial cells and fibroblasts grown in culture and to their extracellular matrices. The interaction was measured in basal conditions and in the presence of the chemotactic effector, formyl-methionyl-leucyl-phenylalanine (FMLP at the concentration of 10 7M). Adhesion was expressed by the number of adherent PMNs/mm2 on a histological specimen. Moreover, we have adapted a program for image analysis to quantify neutrophil adhesion. Three times more PMNs adhered to matrices than to monolayers, and adherence could be increased by the presence of 10-7M FMLP, except in the case of fibroblast monolayers. We found a good correlation between microscopic observation and computerised image analysis measuring PMN adhesiveness to extracellular matrices.

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