IMMUNOFLUORESCENT AND HISTOLOGIC FINDINGS IN THE HEMOLYTIC UREMIC SYNDROME

PEDIATRICS ◽  
1971 ◽  
Vol 47 (2) ◽  
pp. 352-359
Author(s):  
Marc Gervais ◽  
John B. Richardson ◽  
Jane Chiu ◽  
Keith N. Drummond
Keyword(s):  
Endothelial Cells ◽  
Basement Membrane ◽  
Hemolytic Uremic Syndrome ◽  
Vascular Pathology ◽  
Immune Mechanisms ◽  
Glomerular Capillary ◽  
Subendothelial Space ◽  
Uremic Syndrome ◽  
Glomerular Capillaries

Pathologic and immunopathologic studies were done in four patients with the hemolytic uremic syndrome. The principal lesions involved the endothelial and subendothelial regions of the renal arterioles and of the glomerular capillaries. The endothelial cells were swollen and, in the case of the glomerular capillary loops, separated from the basement membrane by an accumulation of material in the subendothelial space. In contrast to the glomerular capillaries, the endothelial changes in the renal arterioles were associated with a striking deposition of fibrinogen or its derivatives. No evidence for the operation of immune mechanisms of the type known to be associated with the development of vascular pathology was found to account for the microangiopathy.

scholarly journals ELECTRON MICROSCOPY OF THE AVIAN RENAL GLOMERULUS

1957 ◽  
Vol 3 (2) ◽  
pp. 183-192 ◽  
Author(s):  
R. K. F. Pak Poy ◽  
J. S. Robertson
Keyword(s):  
Electron Microscopy ◽  
Basement Membrane ◽  
Thin Sheet ◽  
Cell Mass ◽  
Central Cell ◽  
Dense Layer ◽  
Central Mass ◽  
Capillary Basement Membrane ◽  
Glomerular Capillary ◽  
Glomerular Capillaries

Electron microscopy of sections of chicken glomeruli shows them to possess a large central cell mass, occupying the hilum and the centre of the glomerulus, and continuous with the adventitia of the afferent and efferent arterioles. The glomerular capillaries form a much simpler system than in mammals and are spread over the surface of the central cell mass. Between the capillaries the mass is limited externally by the major component of the glomerular capillary basement membrane, which continues over the surface of the mass from one capillary to the next. Projections of the central cell mass characteristically form the support for glomerular capillaries, and smaller knobs of the central mass may project actually into the lumen of the capillaries, but always carry a layer of endothelial cytoplasm before them. They are never in direct contact with blood. The basement membrane of the glomerular capillary loop has a central dense layer and two lateral less dense layers as in mammals. The central dense layer is continuous with similar appearing dense material in the intercellular spaces of the adventitiae of the arterioles, and also with that of the central cell mass. The two less dense layers can also be traced into direct continuity with the less dense regions of this intercellular substance. The endothelial cytoplasm is spread as a thin sheet over the inner surface of the capillary basement membrane, and shows scattered "pores" resembling those described in mammals. Epithelial cells with interlacing pedicels are at least as prominent as those in mammals. Bowman's capsular membrane also possesses three layers similar to but less wide than those of the capillary basement membrane, and all three layers can be traced into continuity with the dark and light regions of the intercellular material of the adventitial cells of the arterioles, and beyond them with that of the central cell mass. At the hilum Bowman's capsular membrane also fuses with the capillary basement membrane.

Anti-factor H autoantibodies and hemolytic uremic syndrome: role of the C-terminus of factor H for activity on endothelial cells

2007 ◽  
Vol 44 (1-3) ◽  
pp. 266
Author(s):  
Mihály Józsi ◽  
Stefanie Strobel ◽  
Martin Oppermann ◽  
John D. Lambris ◽  
Peter F. Zipfel
Keyword(s):  
Endothelial Cells ◽  
Hemolytic Uremic Syndrome ◽  
Factor H ◽  
C Terminus ◽  
Uremic Syndrome ◽  
Factor H Autoantibodies

scholarly journals Thrombotic Thrombocytopenic Purpura and Sporadic Hemolytic-Uremic Syndrome Plasmas Induce Apoptosis in Restricted Lineages of Human Microvascular Endothelial Cells

Blood ◽  
1997 ◽  
Vol 89 (4) ◽  
pp. 1224-1234 ◽  
Author(s):  
Debashis Mitra ◽  
Eric A. Jaffe ◽  
Babette Weksler ◽  
Katherine A. Hajjar ◽  
Carl Soderland ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Hemolytic Uremic Syndrome ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Apoptotic Cell ◽  
Umbilical Vein ◽  
Thrombocytopenic Purpura ◽  
Related Disorder ◽  
Uremic Syndrome ◽  
Vessel Coronary Artery

Abstract Thrombotic thrombocytopenic purpura (TTP) and sporadic hemolytic-uremic syndrome (HUS) are thrombotic microangiopathies that occur in the absence of an inflammatory response. Ultrastructural features of tissues involved in TTP/sporadic HUS suggest an apoptotic process. Consistent with these findings, we observed that TTP plasmas induce apoptosis in primary human endothelial cells (EC) of dermal microvascular but not umbilical vein origin (Laurence et al, Blood 87:3245, 1996). We now document the ability of plasmas from both TTP and sporadic HUS patients, but not from a patient with childhood/diarrhea-associated HUS, to induce apoptosis and expression of the apoptosis-associated molecule Fas (CD95) in restricted lineages of microvascular EC. EC of small vessel dermal, renal, and cerebral origin were susceptible to induction of Fas and an apoptotic cell death. In contrast, microvascular EC of pulmonary and hepatic origin, as well as EC of a large vessel, coronary artery, were resistant to both processes. This dichotomy parallels the in vivo pathology of TTP/sporadic HUS, with notable sparing of the pulmonary and hepatic microvasculature. Apoptotic EC also had some features of a procoagulant phenotype, including depressed production of prostaglandin I2 (prostacyclin). These phenomena support the pathophysiologic significance of microvascular EC apoptosis in TTP, extend it to a related disorder (sporadic HUS), and suggest consideration of apoptosis inhibitors in the experimental therapeutics of these syndromes.

scholarly journals Complement Activation and Thrombotic Microangiopathies

2019 ◽  
Vol 14 (12) ◽  
pp. 1719-1732 ◽  
Author(s):  
Marta Palomo ◽  
Miquel Blasco ◽  
Patricia Molina ◽  
Miquel Lozano ◽  
Manuel Praga ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Hemolytic Uremic Syndrome ◽  
Acute Phase ◽  
Complement Activation ◽  
Hellp Syndrome ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Malignant Hypertension ◽  
Clinical Relapse ◽  
Thrombotic Microangiopathies ◽  
Uremic Syndrome

Background and objectivesAtypical hemolytic uremic syndrome is a form of thrombotic microangiopathy caused by dysregulation of the alternative complement pathway. There is evidence showing complement activation in other thrombotic microangiopathies. The aim of this study was to evaluate complement activation in different thrombotic microangiopathies and to monitor treatment response.Design, setting, participants, & measurementsComplement activation was assessed by exposing endothelial cells to sera or activated-patient plasma—citrated plasma mixed with a control sera pool (1:1)—to analyze C5b-9 deposits by immunofluorescence. Patients with atypical hemolytic uremic syndrome (n=34) at different stages of the disease, HELLP syndrome (a pregnancy complication characterized by hemolysis, elevated liver enzymes, and low platelet count) or severe preeclampsia (n=10), and malignant hypertension (n=5) were included.ResultsAcute phase atypical hemolytic uremic syndrome–activated plasma induced an increased C5b-9 deposition on endothelial cells. Standard and lower doses of eculizumab inhibited C5b-9 deposition in all patients with atypical hemolytic uremic syndrome, except in two who showed partial remission and clinical relapse. Significant fibrin formation was observed together with C5b-9 deposition. Results obtained using activated-plasma samples were more marked and reproducible than those obtained with sera. C5b-9 deposition was also increased with samples from patients with HELLP (all cases) and preeclampsia (90%) at disease onset. This increase was sustained in those with HELLP after 40 days, and levels normalized in patients with both HELLP and preeclampsia after 6–9 months. Complement activation in those with malignant hypertension was at control levels.ConclusionsThe proposed methodology identifies complement overactivation in patients with atypical hemolytic uremic syndrome at acute phase and in other diseases such as HELLP syndrome and preeclampsia. Moreover, it is sensitive enough to individually assess the efficiency of the C5 inhibition treatment.

Involvement of the fractalkine pathway in the pathogenesis of childhood hemolytic uremic syndrome

Blood ◽  
2006 ◽  
Vol 109 (6) ◽  
pp. 2438-2445 ◽  
Author(s):  
María Victoria Ramos ◽  
Gabriela C. Fernández ◽  
Natasha Patey ◽  
Pablo Schierloh ◽  
Ramón Exeni ◽  
...  
Keyword(s):  
Renal Failure ◽  
Endothelial Cells ◽  
Hemolytic Uremic Syndrome ◽  
Cell Damage ◽  
Mononuclear Leukocytes ◽  
Selective Depletion ◽  
Inflammatory Processes ◽  
Uremic Syndrome ◽  
Globotriaosyl Ceramide ◽  
Postdiarrheal Hemolytic Uremic Syndrome

Abstract Thrombotic microangiopathy and acute renal failure are cardinal features of postdiarrheal hemolytic uremic syndrome (HUS). These conditions are related to endothelial and epithelial cell damage induced by Shiga toxin (Stx) through the interaction with its globotriaosyl ceramide receptor. However, inflammatory processes contribute to the pathogenesis of HUS by sensitizing cells to Stx fractalkine (FKN), a CX3C transmembrane chemokine expressed on epithelial and endothelial cells upon activation, is involved in the selective migration and adhesion of specific leukocyte subsets to tissues. Here, we demonstrated a selective depletion of circulating mononuclear leukocytes expressing the receptor for FKN (CX3CR1) in patients with HUS. We found a unique phenotype in children with HUS distinct from that seen in healthy, uremic, or infected controls, in which monocytes lost CX3CR1, down-modulated CD62L, and increased CD16. In addition, the CD56dim natural killer (NK) subpopulation was decreased, leading to an altered peripheral CD56dim/CD56bright ratio from 10.0 to 4.5. It is noteworthy that a negative correlation existed between the percentage of circulating CX3CR1+ leukocytes and the severity of renal failure. Finally, CX3CR1+ leukocytes were observed in renal biopsies from patients with HUS. We suggest that the interaction of CX3CR1+ cells with FKN present on activated endothelial cells may contribute to renal injury in HUS.

scholarly journals THE GLOMERULUS IN EXPERIMENTAL RENAL DISEASE IN RATS AS OBSERVED BY LIGHT AND ELECTRON MICROSCOPY

1955 ◽  
Vol 102 (5) ◽  
pp. 573-580 ◽  
Author(s):  
Carolyn F. Piel ◽  
Luther Dong ◽  
F.W.S. Modern ◽  
Joseph R. Goodman ◽  
Roger Moore
Keyword(s):  
Electron Microscopy ◽  
Endothelial Cells ◽  
Basement Membrane ◽  
Light Microscopy ◽  
Light And Electron Microscopy ◽  
Electron Microscopic ◽  
Crescent Formation ◽  
Colloidal Iron ◽  
Narrow Channels ◽  
Glomerular Capillary

Nephrotoxic serum disease in rats has been studied by light and electron microscopy from 1 hour to 10 weeks after production of the disease. By light microscopy leucocytic infiltration of the glomerular capillary was observed between the 3rd and 6th hour. At 6 hours an increase in colloidal iron-positive material was observed coating the extraluminal surface of the capillaries. Also at this time swelling of the endothelial cells becomes prominent. By 72 hours, thickening of the basement membrane was observed. Glomerular capillary thrombi were observed in approximately half the tissue examined in the first 2 weeks of disease. 50 per cent of the animals showed severe chronic lesions, exudation into the capsular space, crescent formation, and obliteration of glomeruli. At 1 hour electron microscopic pictures showed that osmophilic material may line the foot processes of the epithelial cells and obliterate all but narrow channels of the space between the feet. By 6 hours thickening of the basement membrane was prominent. This change persisted throughout 10 weeks of observation. The tissue from animals which had severe chronic alterations by light microscopy revealed changes which could not be interpreted at this time.

Binding and transfer of verocytotoxin by polymorphonuclear leukocytes in hemolytic uremic syndrome

Blood ◽  
2000 ◽  
Vol 95 (11) ◽  
pp. 3396-3402
Author(s):  
D. Maroeska W. M. te Loo ◽  
Leo A. H. Monnens ◽  
Thea J. A. M. van der Velden ◽  
Mario A. Vermeer ◽  
Frank Preyers ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Hemolytic Uremic Syndrome ◽  
Polymorphonuclear Leukocytes ◽  
Cell Damage ◽  
Binding Studies ◽  
Single Class ◽  
Target Organs ◽  
Uremic Syndrome ◽  
Human Polymorphonuclear Leukocytes

The hemolytic uremic syndrome (HUS) is the most common cause of acute renal failure in children. The role of a verocytotoxin (VT)-producing Escherichia coli has been strongly implicated in the epidemic form of HUS. Although direct toxicity of VT on glomerular endothelial cells has been demonstrated, it remained still unclear how the VT is transported from the intestine to the target organs. In this study we demonstrate that VT, when incubated in whole blood, binds rapidly and completely to human polymorphonuclear leukocytes (PMNs) and not to other components of blood. Binding studies with125I-VT-1 showed a single class of binding sites on freshly isolated, nonstimulated human PMNs. TheKd of VT-binding to PMNs was 10-8 mol/L, 100-fold less than that of the VT-receptor globotriaosylceramide. On incubation of VT-preloaded PMNs with human glomerular microvascular endothelial cells (GMVECs), transfer of VT-1 to the endothelial cells occurred. Incubation of nonstimulated GMVECs with VT-preloaded PMNs, but not with PMNs or VT-1 alone, caused inhibition of protein synthesis and cell death. Our data are in concert with a role of PMNs in the transfer of VT from the intestine to the kidney endothelium. This transfer occurs by selective binding to a specific receptor on PMNs and subsequent passing of the ligand VT to the VT-receptor on GMVECs, which causes cell damage. This new mechanism further underpins the important role of PMNs in HUS.

scholarly journals Characterization of multiple quinine-dependent antibodies in a patient with episodic hemolytic uremic syndrome and immune agranulocytosis

Blood ◽  
1992 ◽  
Vol 80 (1) ◽  
pp. 241-248 ◽  
Author(s):  
DF Stroncek ◽  
GM Vercellotti ◽  
DE Hammerschmidt ◽  
DJ Christie ◽  
RA Shankar ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Hemolytic Uremic Syndrome ◽  
Umbilical Vein ◽  
Protein A ◽  
Platelet Glycoprotein ◽  
Staphylococcal Protein A ◽  
Capture Assay ◽  
Uremic Syndrome ◽  
Neutrophil Aggregation ◽  
Umbilical Vein Endothelial Cells

Abstract A 23-year-old woman experienced six distinct episodes of severe combined neutropenia and thrombocytopenia. At least one of the episodes was accompanied by hemodialysis-requiring acute renal failure and fragmentation hemolysis (hemolytic uremic syndrome [HUS]). In retrospect, all episodes were probably associated with the ingestion of quinine. Quinine-dependent antibodies to platelets, neutrophils, T lymphocytes, and red blood cells (RBCs) were detected in the patient's serum. By a monoclonal antibody antigen capture assay, the patient's serum contained IgG antibodies, which in the presence, but not absence, of quinine reacted with platelet glycoprotein (GP) complexes Ib/IX and IIb/IIIa, but not Ia/IIa. By immunoprecipitation assay, the serum, after addition of quinine, reacted strongly with an 85-Kd neutrophil membrane protein and weakly with 130- and 60-Kd moieties. Serum adsorbed with RBCs in the presence of quinine continued to react with platelets and neutrophils, and serum that was absorbed with platelets continued to react with neutrophils and RBCs, indicating that the antigenic targets were different on platelets, neutrophils, and RBCs. Since platelets and endothelial cells share some antigens, we tested patient serum for antibodies to human umbilical vein endothelial cells (HUVEC); no quinine-dependent antibodies to HUVEC were detected. However, her quinine-dependent antibodies not only bound to platelets and neutrophils, but also activated neutrophils. Thus, the patient's serum with quinine aggregated neutrophils, but neither agent alone caused activation. Moreover, the patient's serum with quinine (but not without) augmented the adherence of neutrophils to HUVEC. Treatment of the patient's serum with staphylococcal protein A removed the quinine neutrophil aggregation cofactor, suggesting it was due to IgG. In both neutrophil aggregation and adherence assays, decomplementation of the patient's serum markedly blunted its effect. Furthermore, the patient's serum failed to aggregate formalin-inactivated neutrophils, suggesting neutrophil activation, probably by activated complement, was necessary for aggregation and adhesivity to endothelium. We conclude that our patient's neutropenia, thrombocytopenia, lymphopenia, and anemia were due to quinine-dependent antibodies, and that these antibodies recognized epitopes that were different in the three target cell populations. We further suggest that HUS was likely secondary to the activation and adhesion of neutrophils to endothelium.

Sign in / Sign up

Export Citation Format

Share Document