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At least 19 recordsLinked to original sources
PubMed1975

The relation between connective tissue cells and intercellular substances, including basement membranes.

Basement membranes are distributed widely in the body forming an extracellular matrix for epithelial and endothelial cells. The collagenous and glycoprotein constituents of basement membranes are synthesized by these two cell types. Disturbance of the interactions between basement membranes and their associated epithelial and endothelial cells can lead to the pathological changes seen in diseases involving basement membranes. These changes are illustrated here by reference to glomerulonephritis induced by the deposition of immune complexes in the glomerulus of the kidney, and chronic inflammatory changes occurring in the lung after inhalation of asbestos. In these diseases basement membrane changes can occur in several ways. Hydrolytic enzymes released from inflammatory cells degrade basement membranes while other constituents by epithelial and endothelial cells. Alternatively the physical separation of epithelial and endothelial cells from their basement membrances by space-occupying substances such as immune complexes can interfere with feedback mechanisms leading to synthesis of basement membrane constituents and cell proliferation. Studies of these pathological changes at a cellular level should shed new light on the ways in which cells interact with their pericellular environment.

Asbestos↗
PubMed1978

Electron microscopy of nephropathia epidemica. Renal tubular basement membrane.

Tubular basement membranes in kidney biopsies from 18 patients with nephropathia epidemica were studied by electron microscopy. Both in the cortex and in the medulla there was splitting of the basement membrane. Thickened basement membrane around occasional tubules contained membrane vesicles, usually empty but also with a core and a diameter of approximately 180 nm. Membranous convoluted structures and light finely fibrillar areas in the basement membranes were seen. Splitting of the basement membrane was most prominent in the medulla, and the membrane was filled with round to oval particles 55 to 470 nm in diameter. Of the possible mechanisms of damage at the basement membrane level in this disease, the findings suggest liberation of antigen from the tubular cells and reaction of circulating antibodies with the antigen in the basement membrane.

Adolescent↗
PubMed1976

Platelet interaction with human umbilical cord vascular basement membrane.

The basement membrane of the human umbilical vein was studied by electron microscopy with respect to its ultrastructure, susceptibility to digestion by collagenase or trypsin, and reactivity with human platelets. Electron microscopic examination of this vessel showed a continuous reticulated basement membrane which morphologically resembled those of mammalian capillaries and rabbit heart valves. The vascular endothelium was removed by freezing and thawing, thus uncovering the underlying connective tissue. The vessels were sliced into rings which were incubated with collagenase or trypsin. The basement lamella appeared to be susceptible to digestion by either enzyme. Platelet interaction with exposed vascular basement mambrane was studied by rotating frozen-thawed everted and noneverted rings in anticoagulated whole human blood. In heparinized or citrated blood, large aggregates of degranulated platelets adhered to collagenous controls; in contrast, the test rings with exposed basement membrane were partially covered with a monolayer of platelets which appeared to retain discoid or spherical shape and granules. In EDTA-anticoagulated blood, the collagen control rings accumulated a platelet monolayer, whereas little or no adhesion occurred on the basement membrane surface. In this system the basement membrane of the human umbilical vein appears to be a poor platelet reactive surface as compared to collagen.

Basement Membrane↗
PubMed1975

Basement membranes: structural and biosynthetic considerations.

Basement membranes are extracellular matrices synthesized by a variety of cells including the basal cells of the epidermis; the respiratory, gastrointestinal, and glandular epithelium; the capillary endothelium; the epithelial cells of the glomerulus, the renal tubule, and the lens capsule; and the endothelium of Descemet's membrane. Basement membranes in the mature animal are free of lipids, DNA, and proteoglycans and are composed of dissimilar protein subunits. One of these is a procollagen-like molecule associated with a noncollagenous matrix glycoprotein. The proportion of the latter component varies among basement membranes. These various subunits are stabilized by hydrogen bonds, disulfide bonds, and aldehyde-derived cross-links which are so extensive that they render the basement membranes highly insoluble. Immunochemical studies indicate three distinct antigenic components which correspond to the collagenous moiety, its nonhelical extension, and the matrix glycoprotein. The collagen component of basement membranes, free of the nonhelical extension, is composed of three identical alpha-chains. It is highly rich in hydroxylysine, 3- and 4-hydroxyproline and contains 4 to 8 residues of half-cystine. It contains 38 residues of glucosyl-galactosyl-hydroxylysine per chain and minimal amounts of mannose, glucosamine, and fucose. Newly synthesized basement membrane collagen is secreted in the extracellular space as the precursor molecule "procollagen." This molecule does not undergo conversion to collagen but interacts with the matrix glycoprotein to give rise to the appropriate structure.

Amino Acids↗
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↗
PubMed1977

Mucopolysaccharide heterogeneity of the reptilian kidney basement membranes.

The kidney basement membranes of fifteen different reptiles from marine, terrestrial, desert, amphibious and fresh-water habitats have been analysed for their mucopolysaccharide contents histochemically, employing well-known and recent techniques. Capsular and tubular basement membranes possess only neutral mucopolysaccharides; on the other hand glomerular basement membrane possesses both neutral and acidic (sialic acid) mucopolysaccharides. The concentration of different mucopolysaccharides seems to be dependent on the type of habitat. Their possible physiological significance in the kidney function is discussed in great details.

Animals↗
PubMed1978

Cellular reactivity to altered glomerular basement membrane in glomerulonephritis.

Glomerular basement membrane may be altered during glomerulonephritis, exposing antigens that are recognized as foreign. Immunochemical studies suggest that removal of peripheral glycopeptides from the basement membrane with glycosidase mimics this pathogenetic event. To examine these hypotheses, we studied 24 patients with biopsy-proved glomerulonephritis by means of the lymphocyte-blast-transformation assay. Three preparations of normal glomerular basement membrane were used: two mimicked the native state for the peripheral glycopeptides, and one was altered by glycosidases. Results showed minimal differences in responses to native glomerular basement-membrane preparations among patients with glomerulonephritis and control groups. However, patients with glomerulonephritis had a significant blastogenic response to the glycosidase-treated glomerular basement membrane as compared to patients with nonglomerular renal disease and normal controls (P less than 0.0005). These studies suggest that cellular reactivity to altered glomerular basement-membrane antigens can be detected in certain forms of progressive glomerulonephritis.

Antigens↗
PubMed1976

The role of hydroxylation of proline in the antigenicity of basement membrane collagen.

Rabbit antibodies to bovine basement membrane collagen were used to compare the antigenic determinants of rat parietal yolk sac basement membrane [14C]procollagen with [14C]protocollagen. Basement membrane [14C]protocollagen was found to be less antigenic than basement membrane [14C]procollagen. Hydroxylation of basement membrane [14C]protocollagen, either intracellularly or in vitro with protocollagen prolyl hydroxylase, resulted in restoration of antigenicity. The difference in antigenicity observed between basement membrane [14C]procollagen and basement membrane [14C]protocollagen appeared to depend primarily upon the presence of hydroxyproline in the collagen molecule. Glucosylgalactosylhydroxylysine was found to be unimportant for antigenicity.

Animals↗
PubMed1979

Immunochemical study on basement membrane (type IV) collagens.

Basement membrane (type IV) collagens were extracted from a mouse tumour with acetic acid and from human placenta after limited enzymatic digestion. Antisera were produced against both collagens in rabbits and guinea-pigs and examined by various assays. These antisera were found to be specific for basement membrane collagen and showed little or no cross-reactions with the interstitial collagens, types I, II and III or with human placenta collagen consisting of alpha A and alpha B chains. Varying degrees of cross-reaction were observed between antisera to human and mouse type IV collagen. Immunochemical analyses demonstrated the presence of three distinct determinants in the tumour type IV collagen. Rabbit antisera against this antigen reacted with either collagenase-resistant segments or with a collagenous, disulphide-bonded segment (P3). Guinea-pig antisera recognized primarily antigenic determinants in the P3 segment. Antisera to placenta type IV collagen reacted with another collagenous, pepsin fragment (P1) which lacks disulphide bonds. These antisera showed complete cross-reaction with collagenous alpha 1 (IV) chains prepared from pepsin-digests of human placenta and bovine lens capsule.

Animals↗
PubMed1978

Membranous glomerulonephritis associated with anti-tubular and anti-alveolar basement membrane antibodies.

The renal biopsy of a 3-year old boy with complete Fanconi syndrome showed the association of a membranous glomerulonephritis with severe tubulointerstial changes. Immunofluorescence microscopy disclosed linear and granular deposits of Ig along tubular basement membranes. The presence of anti-tubular basement membrane antibodies in the patient's serum was demonstrated by indirect immunofluorescence and radioimmunoassay. The child also developed pulmonary involvement associated with episodes of acute anemia. Anti-alveolar basement membrane antibodies were detected by indirect immunofluorescence. The present case is the first reported example of auto-immune disease characterized by the presence of anti-tubular and alveolar basement membrane antibodies associated with an immune complex glomerulonephritis.

Autoantibodies↗
PubMed1975

Studies of normal and nephritic rat glomerular basement membrane.

Solubilization of the normal glomerular basement membrane with various solvents revealed that the material is held together by hydrogen and disulfide linkages as well as ionic salt bridges which ionize at around pH 10.0. Pronase digestion indicated that differences in susceptibility to enzyme digestion exist between normal and nephritic membrane. Titration of a urea-insoluble material indicated that some alteration must have taken place in the association between various components of the nephritic basement membrane. Chemical analysis of alkali-solubilized fractions suggested that greater alkali susceptibility of the nephritic material may be present. A collagen-like material resembling both tendon and dog basement membrane collagen in its amino acid composition was isolated. It contained 10% hexose, but in addition to glucose and galactose, mannose was also detected. A glycopeptide fraction obtained by pronase and collagenase digestion has a carbohydrate composition similar to the collagen-like material above. These substances probably represent incompletely digested fragments of the basement membrane.

Amino Acids↗
PubMed1979

Interaction of bovine platelets with bovine glomerular basement membrane.

The interaction of bovine platelets with bovine glomerular basement membrane has been studied by aggregometry, transmission and scanning electron microscopy and measurement of [3H] serotonin release. In the absence of added calcium platelets adhere to basement membrane but fail to undergo the release reaction or aggregation. In the presence of 0.2-0.5 mM calcium release of serotonin and complete aggregation of the platelets are observed when sufficient basement membrane is present. Platelets were strongly adhered to the basement membrane surface, the platelet surface in the aggregates closely following the surface of the basement membrane. Platelet morphology in aggregates with basement membrane closely resembled that of platelets from collagen-induced aggregates. Basement membrane differed from collagen in its requirement for calcium for the aggregation and release reactions. In addition purified basement membrane was 1.5-3 fold less active on a weight basis than bovine tendon collagen in promoting aggregation.

Animals↗
PubMed1977

The ultrastructural histochemistry of the basement membranes of the exocrine pancreas.

The basement membranes in the exocrine pancreas were examined by routine electron microscopy, by fixation for electron microscopy with a glutaraldehyde-tannic acid solution and by staining for ultrastructural demonstration of mucosubstances with the dialyzed iron, high iron diamine, ruthenium red and Concanavalin A-horseradish peroxidase procedures. The basement membranes are considered from morphologic and histochemical observations to consist of an inner lamina lucida, an intermediate lamina densa and an outer lamina diffusa. Sulfated mucosubstance was found in the lamina diffusa of the basement membrane of all epithelial cells and capillary endothelial cells but was encountered in the lamina lucida of the duct cells exclusively. Bridging structures, presumably polypeptides, were also seen connecting the lamina densa and the basal plasma membrane in specimens fixed with the glutaraldehydetannic acid solution. The findings demonstrated that the histochemical and morphological qualities of the basement membrane are uniform of a given cell type but differ considerably among the several cell types in the pancreas.

Animals↗
PubMed1976

Removal of basement membrane in the involuting breast.

Morphologic and immunohistochemical studies by light and electron microscopy indicated that basement membrane was removed during the process of involution of the murine breast. Removal of the basement membrane started 2 days postweaning, was maximal at 4 days, and correlated with degeneration of epithelial cells. There was no evidence of phagocytosis of basement membrane, so the removal of this antigen was attributed to enzymatic hydrolysis. To determine the activity of breast homogenate on the specific basement membrane antigen, insoluble basement membrane embedded in agarose gels was incubated with breast liver and kidney homogenates. When basement membrane antigen was demonstrated by the specific antibody, it was found that breast homogenate solubilized basement membrane but liver and kidney failed to solubilize basement membrane. To quantify the reaction and determine some of the characteristics of the responsible enzyme(s), insoluble basement membrane was labeled with 125I and the release of radioactivity into the supernatant following incubation with extracts of involuting breast indicated hydrolysis of basement membrane. Extracts of breast homogenate extensively hydrolyzed labeled basement membrane if naturally occurring inhibitors were removed by previous washing, whereas liver or kidney extracts prepared in a similar manner were devoid of activity. The hydrolysis of basement membrane was time and concentration dependent and had a pH optimum. The reaction was blocked by prior heating of the extract at 100 degrees C. for 30 minutes, removal of divalent cations, and presence of diisopropylfluorophosphate (a specific serine esterase inhibitor); prolonged dialysis failed to remove the hydrolytic activity. It is concluded that an enzyme system present in the involuting breast is capable of basement membrane hydrolysis

Animals↗
PubMed1979

Lectin-like activity of components extracted from human glomerular basement membrane.

Different fractions of human glomerular basement membranes have been isolated by enzymatic and chemical methods. These fractions were analyzed for their chemical structure and biological activity. The hypothesis that human glomerular basement membrane glycopeptide fractions related to collagenous sequences could act as a lectin-like substance was explored; in fact, extracellular glycoprotein factors play a role in cell-cell interactions and cell adhesion. These collagenous glycopeptides agglutinate human transformed or embryonic cells within 2 hr. The cell agglutination is inhibited by the following sugars: N-acetylglucosamine, N-acetylgalactosamine, and N-acetylneuraminic acid. In addition, the rapid cytoagglutination is followed by a cell spreading effect after a further 20-hr incubation. These data led to the postulate that the maintenance of tissue differentiation is governed by the interaction of cells with peculiar sites of the basement membrane consisting of a proteolysis-resistant association between collagen and matrix glycoprotein.

Agglutination Tests↗
PubMed1979

Thickness and volume constants and ultrastructural organization of basement membrane (lens capsule).

1. The basement membrane of the crystalline lens of the rat has been found to have the following elastic constants: a Young's Modulus of elasticity of 0.56 +/- 0.38 x 10(6) Nm-2 at low stress and 11.3 +/- 1.9 x 10(6) Nm-2 at rupture, an ultimate stress of 28.8 +/- 4.5 x 10(5) Nm-2, and a maximum percentage elongation of 41.3 +/- 5.8. 2. The ratio of initial thickness of the membrane to the thickness at the point of rupture is 0.271 +/- 0.02 while the similar ratio for volume is 0.461 +/- 0.031. 3. Electron microscopic observations of ultrasonicated fragments of the entire membrane show long filaments in parallel arrays and sheets. The filaments show a periodicity of 3.7 nm and a spacing of 3.5 nm. 4. Electron microscopic observations of collagenase-treated membrane show a poorly staining matrix associated with separate short straight non-periodic filaments some 2.5 nm in diameter. In addition strands project from the ends of the filaments with a diameter of between 0.5 and 1.0 nm. 5. A model is proposed which consists of these filaments, composed of between three and five parallel strands, some 0.8 nm in diameter, wound in a superhelix. 6. The model predicts satisfactorily thickness and volume changes in the membrane when subjected to stress, and also indicates that the filaments would have a similar Young's Modulus of elasticity and ultimate stress to those of collagen. 7. If the basement membrane of the smallest retinal capillaries is subjected to a change of pressure of only 5 mmHg within the vessel lumen, then the membrane is likely to undergo some 30% reduction in thickness.

Animals↗