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PubMed1999

Surface bound plasmin promotes migration of Streptococcus pneumoniae through reconstituted basement membranes.

Penetration of basement membrane is believed to be an essential step in the pathogenesis of bacterial meningitis. Consequently Streptococcus pneumoniae strains were tested for their ability to adhere to reconstituted basement membrane (Matrigel) and in a proceeding step penetrate this membrane by the use of surface activated plasmin. A majority of S. pneumoniae strains tested were found to adhere to reconstituted basement membrane as well as to the purified laminin component. Three out of seventeen strains also adhered to the collagen IV component. All the investigated strains also demonstrated a capacity to bind plasminogen with up to 42,000 plasminogen binding sites per bacterium as estimated by Scatchard analysis. Two strains selected for optimal adhesion and plasminogen binding were further tested for basement membrane penetration using a dual chamber model. Our data show that penetration was achieved within 3-4 h in the presence of plasminogen whereas without plasminogen no strain was able to penetrate during a 21 h incubation. The results suggest a potential role of surface associated plasminogen in bacterial penetration of basement membranes and extracellular matrix.

Bacterial Adhesion↗
PubMed1985

Lack of heparan sulfate proteoglycan in a discontinuous and irregular placental basement membrane.

A discontinuous basement membrane of variable width that surrounds spongiotrophoblast cells of rat placenta was examined for the presence of type IV collagen, laminin, a heparan sulfate proteoglycan, entactin, and fibronectin using monospecific antibodies or antisera and the indirect peroxidase technique. At the level of the light microscope, the basement membrane was immunostained for type IV collagen, laminin, entactin, and fibronectin. Heparan sulfate proteoglycan immunostaining, however, was virtually absent even after pretreatment of sections with 0.1 N acetic acid, pepsin (0.1 microgram/ml) or 0.13 M sodium borohydride. Examination in the electron microscope confirmed the lack of immunostaining for heparan sulfate proteoglycan, whereas the other substances were mainly localized to the lamina densa part of the basement membrane. The absence of heparan sulfate proteoglycan in this discontinuous and irregular basement membrane even though type IV collagen, laminin, entactin, and fibronectin are present, suggests that heparan sulfate proteoglycan may have a structural role in the formation of basement membrane.

Animals↗
PubMed1986

How is the basement membrane attached to the dermis? Stereology of the interlacing fibers at the underface of the dermo-epidermal basement membrane.

A three-dimensional view of the underface of the dermoepidermal basement membrane is provided by scanning electron microscopy and correlated with aspects of optical and transmission electron microscopy. A thin network of interlacing fibers runs parallel to the basement membrane and appears to be attached to it from site to site through loops of anchoring fibers. A model of the attachment of the basement to the dermis is proposed.

Actin Cytoskeleton↗
PubMedDate not supplied

Immunologic cross-reactivity between antisera to group A, type 12 streptococcal cell membrane and human glomerular basement membrane. The effect of age and carbohydrate content.

Antisera to group A, type 12 streptococcal cell membrane and human glomerular basement membrane was evaluated, by indirect immunofluorescence, on adult and neonatal human kidney sections, before and after carbohydrase treatment. Cleavage of GBM carbohydrate potentiated the reactivity of SCM antisera on adult GBM, but not neonatal GBM which in general showed maximal activity without CHOase treatment. Of 22 sera checked 17 showed positive reactivity versus human GBM. Chemical analyses showed that adult GBM contained more carbohydrate than did neonatal GBM, which may explain the observed masking effect.

Adult↗
PubMed1988

Interferon-induced glomerular basement membrane and endothelial cell lesions in mice. An immunogold ultrastructural study of basement membrane components.

Newborn Swiss mice were injected daily for the first week of life with mouse interferon alpha/beta. This treatment resulted in a delay in the maturation of the kidney and the development of glomerular abnormalities. The width of the glomerular basement membrane (GBM) was increased up to tenfold and was characterized by a marked thickening of the endothelial aspect of the GBM. The endothelial cells lining the capillary loops were also abnormal with many dilated regions of the rough endoplasmic reticulum that contained amorphous electron-opaque material. Immunogold studies showed that type IV collagen and laminin/entactin were distributed throughout the thickened GBM, and also within the dilated rough endoplasmic reticulum of the endothelial cells. These results show that the interferon-induced lesion within the glomerulus is associated with an accumulation of normal GBM components and that endothelial cells are involved in this pathologic process.

Animals↗
PubMed1998

Differentiation of a colon cancer cell line on a reconstituted basement membrane in vitro.

Basement membrane, a thin extracellular matrix, functions as a tissue stabilizer that promotes tissue integrity and differentiated phenotype. We studied a human colon cancer cell line, SNU 61, to evaluate its ability to differentiate on basement membrane. Cells were cultured on plastic, reconstituted basement membrane (Matrigel) or polyhydroxyethyl methacrylate (poly HEMA) for 72 h and evaluated by light and electron microscopy. On Matrigel, the cells showed gland formation with highly polarized cells containing basal nuclei and well developed brush border microvilli on the luminal surface. Apoptosis was noted mainly at the luminal side. On electron microscopic examination, numerous long microvilli, abundant cytoplasmic organelles and intercellular junctions were noted in the Matrigel-cultured cells. Intermediate cytoskeletons were scattered in the cytoplasm and existed on the axes of microvilli. Junctional complexes and desmosomes were frequently formed along intercellular spaces. The cells cultured on poly HEMA, on the other hand, were poorly differentiated and contained a few glandular structures with small lumens. Brush border microvilli, characteristic of enterocytic differentiation, were few in number and were developed on the basal surface. Intermediate filaments and microtubules were fewer than in the Matrigel-cultured cells. Carcinoembryonic antigen was expressed on the luminal surface of the Matrigel-cultured cells and in the cytoplasm of the poly HEMA cultured cells. CD44 stained the basolateral surface in the Matrigel-cultured cells, but the basal side was not stained in the poly HEMA cultured cells. These results are consistent with the different localization of microvilli in the Matrigel and in the poly HEMA cultured cells. Our observations suggest that human colon cancer cells on basement membrane can undergo glandular differentiation and that extracellular matrix is an important factor in morphogenesis.

Basement Membrane↗
PubMed1987

The skin basement membrane zone.

The basement membrane zone of skin is a complex, highly compartmentalized structure composed of many distinct antigens. As illustrated in epidermolysis bullosa, alteration in one or more of these antigens may result in abnormal integrity of the dermoepidermal junction, leading to increased mechanical fragility and blister formation. In addition, autoimmunization to basement membrane components, as in the case of bullous pemphigoid and EBA antigens, may result in the development of selected bullous diseases. To date, little is known about the functions and interactions of the antigens identified within human skin basement membrane. It is likely that future studies will provide not only these answers but also additional insight into other diseases associated with basement membrane involvement.

Animals↗
PubMed2005

Distribution of IgG subclasses in a biopsy specimen showing membranous nephropathy with anti-glomerular basement membrane glomerulonephritis: an uncharacteristically good outcome with corticosteroid therapy.

Few occurrences of anti-glomerular basement membrane glomerulonephritis superimposed on membranous nephropathy have been reported; most reported cases began as membranous nephropathy. Little is known about the etiology, pathogenesis, or immunoglobulin G subclasses in glomerular basement membrane deposits in these combined cases. The authors report the case of an elderly patient with apparently simultaneous onset of both membranous nephropathy and anti-glomerular basement membrane glomerulonephritis who had an excellent outcome with only pulse corticosteroid therapy. Successive renal biopsy specimens showed occurrence and disappearance of immunoglobulin G4 deposits in the glomerular basement membrane. Immunoglobulin G subclass analysis was important in recognizing membranous nephropathy underlying the anti-glomerular basement membrane disease.

Aged↗
PubMed1995

Structure and function of basement membranes.

The importance of basement membranes in development and adult tissue function has been inferred from a number of observations. Cells migrate along basement membranes during development, basement membranes are required for the polarization of cells in both the embryo and the adult, and basement membranes serve as substrates for cell adhesion and migration during wound healing and nerve regeneration. The importance of basement membranes in adult tissue function has been directly demonstrated by the genetic diseases caused by mutations in the genes for structural basement membrane components. Examples of such diseases are Alport syndrome and junctional epidermolysis bullosa. Recently, defects in the major laminin variant in muscle, merosin, has been shown to be correlated with muscular dystrophies in man and animals. We are using the dystrophic mutant mouse dy, which lacks laminin-2, to analyze the function of laminin-2 in different tissues. Studies of laminin defects in animals and humans are expected to give new information on the function of basement membrane in general and on laminin in particular. Such information may give directions for future diagnosis and treatment of diseases involving basement membranes.

Aging↗
PubMed1989

[Structure and antigenicity of the glomerular basement membrane].

The glomerular basement membrane is a complex extracellular matrix formed of various molecules which build a supramolecular network. The major structural components are collagen IV, laminin, heparan sulfate proteoglycan, and nidogen/entactin. Cross-reacting antibodies against laminin, nidogen, and collagen IV may occur after several infectious diseases. They are however of doubtful pathogenetic significance. The pathogenetic relevant autoantibodies in Goodpasture's syndrome and rapidly progressive glomerulonephritis with linear immunofluorescence pattern are directed against epitopes which are located on the collagenase resistant C-terminal globule NC1 of collagen IV. The human NC1 globule appears as a hexamer which dissociates into monomers and dimers under various experimental conditions. Dissociation is paralleled by a significant increase in available epitopes. Immunisation with the dissociated NC1 globule initiates a pulmo-renal syndrome in rabbits similar to the human Goodpasture's syndrome. In hereditary nephritis one of the alpha-chains which form the triple-helix of collagen IV seems to be altered within the NC1 region. This may possibly explain the typical morphologic findings in this disease as well as the reduced binding of antiglomerular basement membrane antibodies to basement membranes of kidneys in Alport's syndrome.

Animals↗
PubMed1979

Presence of heparan sulfate in the glomerular basement membrane.

The glomerular basement membrane was subjected to digestion with specific enzymes to determine the chemical nature (sialoglycoproteins, collagenous peptides, or glycosaminoglycans) of the anionic sites previously demonstrated in the laminae rarae. Enzyme digestion was carried out both in situ and in vitro. Kidneys were perfused in situ with enzyme solutions followed by perfusion with fixative containing the cationic dye, ruthenium red, to detect the anionic sites. Glomerular basement membranes were isolated by detergent treatment of glomeruli and incubated with enzyme solutions, followed by incubation with cationized ferritin (pI 7.3-7.5) to label the anionic sites. Only highly purified enzymes free of proteolytic activity were used. The findings were the same both in situ and in vitro. The anionic sites were unaffected by treatment with neuraminidase, chondroitinase ABC, and testicular or leech hyaluronidase. However, they could no longer be demonstrated after digestion with crude heparinase, purified heparitinase, or Pronase or after nitrous acid oxidation. The results demonstrate that the sites contain heparan sulfate since they are removed by treatment with heparitinase and by nitrous acid oxidation-procedures specific for heparan sulfate; and that sialoglycoproteins or other glycosaminoglycans do not represent major components of these sites since the latter are not affected by digestion with neuraminidase and other glycosaminoglycan-specific enzymes. Identical findings were obtained on basement membranes in other locations (Bowman's capsule, tubule epithelium, and endothelium of peritubular capillaries). The presence of heparan sulfate in the glomerular basement membrane is discussed in relation to the charge-selective properties of the glomerular filter and in relation to its potential involvement in various types of glomerular injury.

Animals↗