scholarly journals Fcγ Receptor Iib–Deficient Mice Develop Goodpasture's Syndrome upon Immunization with Type IV Collagen

2000 ◽  
Vol 191 (5) ◽  
pp. 899-906 ◽  
Author(s):  
Akira Nakamura ◽  
Takae Yuasa ◽  
Azusa Ujike ◽  
Masao Ono ◽  
Toshihiro Nukiwa ◽  
...  
Keyword(s):  
Rapidly Progressive Glomerulonephritis ◽  
Pulmonary Hemorrhage ◽  
Basement Membranes ◽  
Collagen Type Iv ◽  
Goodpasture's Syndrome ◽  
Goodpasture’S Syndrome ◽  
Type Iv ◽  
Suitable Animal Model ◽  
And Function

The combination of hemorrhagic pneumonitis and rapidly progressive glomerulonephritis is a characteristic feature of Goodpasture's syndrome (GPS), an autoimmune disease resulting from the interaction of pathogenic anti–collagen type IV (C-IV) antibodies with alveolar and glomerular basement membranes. Lack of a suitable animal model for this fatal disease has hampered both a basic understanding of its etiology and the development of therapeutic strategies. We now report a novel model for GPS using mice deficient in a central regulatory receptor for immunoglobulin (Ig)G antibody expression and function, the type IIB Fc receptor for IgG (FcγRIIB). Mutant mice immunized with bovine C-IV reproducibly develop massive pulmonary hemorrhage with neutrophil and macrophage infiltration and crescentic glomerulonephritis. The distinctive linear, ribbon-like deposition of IgG immune complex seen in GPS was observed along the glomerular and tubulointerstitial membranes of diseased animals. These results highlight the role of FcγRIIB in maintaining tolerance and suggest that it may play a role in the pathogenesis of human GPS.

Seronegative Goodpasture’s syndrome associated with organising pneumonia

2021 ◽  
Vol 14 (2) ◽  
pp. e239390
Author(s):  
Ju Young Bae ◽  
Khalil Ian Hussein ◽  
Eric Leibert ◽  
Herbert M Archer
Keyword(s):  
Kidney Injury ◽  
Final Diagnosis ◽  
Open Lung Biopsy ◽  
Basement Membranes ◽  
Immunofluorescent Staining ◽  
Antibody Testing ◽  
Goodpasture's Syndrome ◽  
Course Of Illness ◽  
Goodpasture’S Syndrome ◽  
Type Iv

Goodpasture’s syndrome is a rare vasculitis associated with anti-glomerular basement membrane (anti-GBM) autoantibodies that target type IV collagen found in the basement membranes of glomeruli and alveoli. We present a case of a 79-year-old man with seronegative Goodpasture’s syndrome with predominant respiratory symptoms and mild acute kidney injury that initially improved. Final diagnosis was made by immunofluorescent staining on open lung biopsy which also revealed concomitant organising pneumonia. The patient underwent treatment with corticosteroids, cyclophosphamide, haemodialysis and plasmapheresis. This was an atypical presentation wherein the patient only exhibited pulmonary symptoms early in the course of illness in the setting of negative anti-GBM antibody serum testing, which made diagnosis challenging. With this case, we emphasise that clinicians should have a high suspicion for Goodpasture’s syndrome in the setting of unexplained severe pulmonary or renal disease despite negative anti-GBM antibody testing.

scholarly journals A dynamic and mosaic basement membrane controls cell intercalation in Drosophila ovaries

Development ◽  
2021 ◽  
Vol 148 (4) ◽  
pp. dev195511
Author(s):  
Véronique Van De Bor ◽  
Vincent Loreau ◽  
Marilyne Malbouyres ◽  
Delphine Cerezo ◽  
Audrey Placenti ◽  
...  
Keyword(s):  
Cell Attachment ◽  
Basement Membranes ◽  
Collagen Type Iv ◽  
Type Iv ◽  
Multiple Origins ◽  
Dynamic Assembly ◽  
Main Component ◽  
And Function ◽  
Cell Intercalation

ABSTRACTBasement membranes (BM) are extracellular matrices assembled into complex and highly organized networks essential for organ morphogenesis and function. However, little is known about the tissue origin of BM components and their dynamics in vivo. Here, we unravel the assembly and role of the BM main component, Collagen type IV (ColIV), in Drosophila ovarian stalk morphogenesis. Stalks are short strings of cells assembled through cell intercalation that link adjacent follicles and maintain ovarian integrity. We show that stalk ColIV has multiple origins and is assembled following a regulated pattern leading to a unique BM organisation. Absence of ColIV leads to follicle fusion, as observed upon ablation of stalk cells. ColIV and integrins are both required to trigger cell intercalation and maintain mechanically strong cell-cell attachment within the stalk. These results show how the dynamic assembly of a mosaic BM controls complex tissue morphogenesis and integrity.

scholarly journals In Situ Localization of Gelatinolytic Activity in the Extracellular Matrix of Metastases of Colon Cancer in Rat Liver Using Quenched Fluorogenic DQ-gelatin

2003 ◽  
Vol 51 (6) ◽  
pp. 821-829 ◽  
Author(s):  
Olaf R.F. Mook ◽  
Claudia Van Overbeek ◽  
Eleonora G. Ackema ◽  
Febe Van Maldegem ◽  
Wilma M. Frederiks
Keyword(s):  
Colon Cancer ◽  
Extracellular Matrix ◽  
Rat Liver ◽  
Collagen Type ◽  
Basement Membranes ◽  
Gelatinolytic Activity ◽  
Collagen Type Iv ◽  
Type Iv

Matrix metalloproteinases (MMPs) such as gelatinases are believed to play an important role in invasion and metastasis of cancer. In this study we investigated the possible role of MMP-2 and MMP-9 in an experimental model of colon cancer metastasis in rat liver. We demonstrated with gelatin zymography that the tumors contained MMP-2 and MMP-9, but only MMP-2 was present in the active form. Immunolocalization of MMP-2 showed that the protein was localized at basement membranes of colon cancer cells and in intratumor stroma, associated with extracellular matrix (ECM) components. However, zymography and immunohistochemistry (IHC) do not provide information on the localization of MMP activity. Therefore, we developed an in situ zymography technique using the quenched fluorogenic substrate DQ-gelatin in unfixed cryostat sections. The application of DQ-gelatin in combination with a gelled medium allows precise localization of gelatinolytic activity. Fluorescence due to gelatinolytic activity was found in the ECM of tumors and was localized similarly to both MMP-2 protein and collagen type IV, its natural substrate. The localization of MMP-2 activity and collagen type IV at similar sites suggests a role of MMP-2 in remodeling of ECM of stroma in colon cancer metastases in rat liver.

Antiglomerular Basement Membrane Disease

2018 ◽  
Vol 39 (04) ◽  
pp. 494-503 ◽  
Author(s):  
Charles Pusey ◽  
Stephen McAdoo
Keyword(s):  
Basement Membrane ◽  
Rapidly Progressive Glomerulonephritis ◽  
Basement Membranes ◽  
Alveolar Hemorrhage ◽  
Type Iv ◽  
Maintenance Immunosuppression ◽  
Life Threatening ◽  
Renal Prognosis ◽  
Function Testing

AbstractAntiglomerular basement membrane (anti-GBM) disease is a rare but life-threatening autoimmune vasculitis that is characterized by the development of pathogenic autoantibodies to type IV collagen antigens expressed in the glomerular and alveolar basement membranes. Once deposited in tissue, these autoantibodies incite a local capillaritis which manifests as rapidly progressive glomerulonephritis (GN) in 80 to 90% of patients, and with concurrent alveolar hemorrhage in ∼50%. A small proportion of cases may present with pulmonary disease in isolation. Serological testing for anti-GBM antibodies may facilitate rapid diagnosis, though renal biopsy is often required to confirm the presence of necrotizing or crescentic GN and linear deposition of autoantibody on the glomerular basement membrane. Alveolar hemorrhage may be evident clinically, or detected on imaging, pulmonary function testing, or bronchoscopy. Prompt treatment with plasmapheresis, cyclophosphamide, and steroids is usually indicated to remove pathogenic autoantibodies, to prevent their ongoing production, and to ameliorate end-organ inflammation. Alveolar hemorrhage is usually responsive to this treatment, and long-term respiratory sequelae are uncommon. Renal prognosis is more variable, though with aggressive treatment, independent renal function is maintained at 1 year in more than 80% of patients not requiring renal replacement therapy at presentation. Relapse in uncommon in anti-GBM disease, unless there is a concomitant antineutrophil cytoplasm antibody (present in 30–40%), in which case maintenance immunosuppression is recommended.

scholarly journals Expression of collagen type IV in human kidney during prenatal development

2020 ◽  
pp. 111-111
Author(s):  
Vladimir Petrovic ◽  
Ivan Nikolic ◽  
Marko Jovic ◽  
Vladimir Zivkovic ◽  
Miodrag Jocic ◽  
...  
Keyword(s):  
Type Iv Collagen ◽  
Collagen Type ◽  
Kidney Tissue ◽  
Volume Density ◽  
Collagen Iv ◽  
Basement Membranes ◽  
Collagen Type Iv ◽  
Type Iv ◽  
Metanephric Kidney ◽  
Collecting System

Background / Aim. Type IV collagen belongs to the group of non-fibrillar collagens and is an important component of the basement membranes where it accounts for approximately 50% of its structural elements. The aim of the paper was to describe the expression and distribution of collagen type IV in embryonic and fetal metanephric kidney, and to determine the volume density of collagen type IV in kidney tissue in each trimester of development. Methods. The material consisted of 19 human embryos/fetuses, in the gestational age from 8th to 37th week. Kidney tissue specimens were routinely processed to paraffin molds and stained with hematoxylin and eosin and immunohistochemically using polyclonal anti-collagen IV antibody. Stained slides were examined using light microscope and images of the selected areas, under different lens magnification were captured with digital camera. Volume density of collagen type IV was determined by using ImageJ 1.48v and a plugin of the software which inserted a grid system with 336 points. For the data comparison One-Way Analysis of Variance was used. Results. Strong collagen IV immunopositivity was seen in all specimens, with a distribution in the basement membranes of urinary bud, parietal leaf of Bowman?s capsule, glomerular basement membrane, basement membrane of interstitial blood vessels, and basement membranes of nephron tubules and collecting ducts. No statistically significant difference in the volume density of type IV collagen was found between the different trimesters of development. Conclusion. The synthesis and secretion of collagen type IV simultaneously follows the development of nephron structures, collecting system and blood vessels. The volume density of collagen type IV remains constant throughout all the trimesters of metanephric kidney development, indicating that it plays a crucial role in normal development of nephron and collecting system structures, as well as in maintaining the normal kidney function.

Specific ablation of the nidogen-binding site in the laminin γ1 chain interferes with kidney and lung development

Development ◽  
2002 ◽  
Vol 129 (11) ◽  
pp. 2711-2722 ◽  
Author(s):  
Michael Willem ◽  
Nicolai Miosge ◽  
Willi Halfter ◽  
Neil Smyth ◽  
Iris Jannetti ◽  
...  
Keyword(s):  
Basement Membrane ◽  
Binding Site ◽  
Lung Development ◽  
Collagen Type Iv ◽  
Developmental Defects ◽  
Type Iv ◽  
And Function ◽  
Kidney Morphogenesis ◽  
Nidogen 1

Basement membrane assembly is of crucial importance in the development and function of tissues and during embryogenesis. Nidogen 1 was thought to be central in the assembly processes, connecting the networks formed by collagen type IV and laminins, however, targeted inactivation of nidogen 1 resulted in no obvious phenotype. We have now selectively deleted the sequence coding for the 56 amino acid nidogen-binding site, γ1III4, within the Lamc1 gene by gene targeting. Here, we show that mice homozygous for the deletion die immediately after birth, showing renal agenesis and impaired lung development. These developmental defects were attributed to locally restricted ruptures in the basement membrane of the elongating Wolffian duct and of alveolar sacculi. These data demonstrate that an interaction between two basement membrane proteins is required for early kidney morphogenesis in vivo.

Diffuse Leiomyomatosis of the Esophagus: Disorder of Cell-Matrix Interaction?

1998 ◽  
Vol 1 (6) ◽  
pp. 543-549 ◽  
Author(s):  
Paul Thorner ◽  
Laurence Heidet ◽  
Fernando Moreno Merlo ◽  
Vern Edwards ◽  
Corinne Antignac ◽  
...  
Keyword(s):  
Collagen Type ◽  
Rare Condition ◽  
Basement Membranes ◽  
Collagen Type Iv ◽  
Cell Periphery ◽  
Matrix Interaction ◽  
Type Iv ◽  
Cell Matrix ◽  
Reverse Pattern ◽  
Genes Encoding

Diffuse leiomyomatosis (DL) is rare condition characterized by proliferation of smooth muscle in the upper gastrointestinal tract. Most cases are associated with X-linked Alport syndrome and have partial deletions in the genes encoding both the α5 and α6 chains of collagen type IV. We studied aspects of cell-matrix interaction of myocytes in an esophagogastrectomy specimen from a 12-year-old patient with DL. Myocytes had central areas of cytoplasmic rarefaction, which were actin positive and desmin poor, with the reverse pattern of staining at the cell periphery. Electron microscopy (EM) showed that the areas of rarefaction consisted of disorganized aggregates of filaments. The basement membranes ranged from thickened to thinned or absent. Immunohistochemical staining for the α1–α4 chains of collagen type IV, the α1, α2, β2, and γ1 chains of laminin, nidogen, type VI collagen, and fibronectin was normal. There was loss of the α5 and α6 chains of collagen type IV and the β1 chain of laminin. Normal staining for α1, α2, α3, α4, α6, α8, and β1 integrins was noted. Staining for α5 integrin varied from normal to reduced or negative in different cells. In DL, a primary abnormality of basement membrane may be associated with disorganization of the contractile apparatus and alterations of certain integrins. This may reflect a disturbance of cell-matrix interactions that play a role in cell differentiation and internal organization.

Macromolecular constituents of basement membranes: a review of current knowledge on their structure and function

1983 ◽  
Vol 61 (8) ◽  
pp. 942-948 ◽  
Author(s):  
Paul G. Scott
Keyword(s):  
Type Iv Collagen ◽  
Current Knowledge ◽  
Heparan Sulphate ◽  
Structural Features ◽  
Structure And Function ◽  
Basement Membranes ◽  
Type Iv ◽  
Type V ◽  
And Function ◽  
Additional Form

Macromolecules which appear to be integral constituents of basement membranes include type IV collagen, the glycoprotein laminin, and heparan sulphate proteoglycan. Another glycoprotein, fibronectin, may occupy an intermediate position between some lining cells and their basement membranes but is not, however, restricted to this location. An additional form of collagen, genetic type V which differs significantly from type IV collagen in structure, appears to be associated with some basement membranes, possibly linking them to underlying connective tissue. The main structural features of each of these macromolecules, as presently understood, are reviewed here as a background to the experimental papers in this "mini-symposium."

scholarly journals Role of myofibroblasts and collagen type IV in patients of IgA nephropathy as markers of renal dysfunction

2010 ◽  
Vol 20 (1) ◽  
pp. 34 ◽  
Author(s):  
RW Minz ◽  
A Bakshi ◽  
S Chhabra ◽  
K Joshi ◽  
V Sakhuja
Keyword(s):  
Renal Dysfunction ◽  
Iga Nephropathy ◽  
Collagen Type ◽  
Collagen Type Iv ◽  
Type Iv

scholarly journals An attempt at quantitation of procollagens I and III and of collagen IV in tooth sections by exposure to the corresponding antibodies followed by 125I-protein A and radioautography.

1980 ◽  
Vol 28 (12) ◽  
pp. 1355-1358 ◽  
Author(s):  
G M Wright ◽  
C P Leblond
Keyword(s):  
Collagen Type ◽  
Protein A ◽  
Collagen Iv ◽  
Basement Membranes ◽  
Collagen Type Iv ◽  
Periodontal Tissue ◽  
Rat Incisor ◽  
Type Iv ◽  
Silver Grains ◽  
Procollagen Iii

The immunoreactivity of procollagen types I and III and of collagen type IV was detected in frozen sections of the growing apical end of rat incisor teeth by an indirect method making use of protein A. The sections were exposed to affinity-purified antibodies against these substances. The bound antibodies were then detected by incubation with radioiodinated protein A, followed by radioautography. This immunoradioautographic approach yielded preparations with low background, in which the reactions could be quantitated by counts of silver grains. The distribution of the radioautographic reactions was essentially the same as that previously observed with direct and indirect peroxidase methods, that is, procollagen I antigenicity predominated in odontoblasts and predentin, with minor amounts in periodontal tissue and pulp; procollagen III antigenicity was present in periodontal tissue and, to a lesser extent, in the pulp; and collagen IV antigenicity was restricted to basement membranes. Moreover, grain counts provided quantitative support for the conclusions on the distribution of procollagen I and III antigenicity.

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