scholarly journals FUNCTIONAL EVIDENCE FOR THE EXISTENCE OF A THIRD CELL TYPE IN THE RENAL GLOMERULUS

1962 ◽  
Vol 13 (1) ◽  
pp. 55-87 ◽  
Author(s):  
Marilyn G. Farquhar ◽  
George E. Palade
Keyword(s):  
Basement Membrane ◽  
Kidney Tissue ◽  
Capillary Wall ◽  
Renal Glomerulus ◽  
Sequence Of Events ◽  
Cytoplasmic Bodies ◽  
Cytoplasmic Vesicles ◽  
Spinous Processes ◽  
Luminal Side ◽  
Peripheral Areas

Two types of cells can be recognized on the luminal side of the glomerular basement membrane: the superficial endothelial cells which directly line the lumen and are comparable to endothelia lining the capillaries of other tissues, and the deep cells, ordinarily not in contact with the lumen, which are distinguished by their long cytoplasmic arms extending for some distance in several directions along the capillary wall, numerous spinous processes, and occasional intraluminal pseudopodia. Experiments carried out with electron-opaque tracers indicated that a functional distinction, based on extent of phagocytosis, can be made between the superficial and deep cells, thus supporting the existence of a distinctive "third" cell (in addition to endothelium and epithelium) in the renal glomerulus. Ferritin, colloidal gold, or thorotrast was administered intravenously to normal and, in the case of ferritin, to nephrotic rats. Kidney tissue was fixed at selected intervals from 1 hour to 10 days after the injection and studied by electron microscopy. Within 1 to 4 hours after tracer administration, the particles which did not traverse the glomerular capillary wall gradually accumulated in the less compact, inner strata of the basement membrane and the large spongy areas of axial regions. After 1 day the concentration of circulating tracer declined and the peripheral areas of the capillaries became relatively free of particles while large accumulations developed in the axial regions. During this period increasing quantities of ferritin were taken up by the deep cells and were found within large and small sized invaginations of their cell membrane or concentrated within cytoplasmic vesicles, vacuoles, multivesicular and dense bodies. At the same time the deep cells showed increased numbers of intraluminal pseudopodia. Within 2 to 4 days the deposits in the spongy areas were cleared and concomitantly increased quantities of tracer appeared in the deep cells within dense cytoplasmic bodies, some of which were more compact than before. When ferritin was given to nephrotic animals the sequence of events was generally the same except that the ferritin deposits at any given period were more massive, their incorporation into the deep cells occurred primarily by means of large pockets 1 to 2 µ in diameter and their clearance from the spongy areas was slower. In normal as well as in nephrotic animals, the phagocytic activity of the superficial endothelium was negligible when compared to that of the deep cells.

scholarly journals GLOMERULAR PERMEABILITY

1961 ◽  
Vol 114 (5) ◽  
pp. 699-716 ◽  
Author(s):  
Marilyn G. Farquhar ◽  
George E. Palade
Keyword(s):  
Nephrotic Syndrome ◽  
Basement Membrane ◽  
Kidney Tissue ◽  
Normal Animal ◽  
High Concentration ◽  
Glomerular Permeability ◽  
Cytoplasmic Matrix ◽  
Filtration Barrier ◽  
Dense Bodies ◽  
Cytoplasmic Vesicles

Ferritin was used as a tracer to investigate glomerular permeability in the nephrotic rat. The results were compared with those previously obtained in normal animals. A nephrotic syndrome was induced by 9 daily injections of the aminonucleoside of puromycin. Ferritin was administered intravenously on the 10th day, and kidney tissue was fixed at intervals of 5 minutes to 44 hours after injection of the tracer and examined by electron microscopy. The observations confirmed that at this stage of the experimental nephrotic syndrome the changes affect predominantly the visceral epithelium (loss of foot processes, reduction and modification of urinary slits, and intracellular accumulation of vacuoles and protein absorption droplets). Less extensive changes were found in other layers (reduction of endothelial fenestrae, an increase in the population of "deep" cells, and a thinning and "loosening" of the basement membrane.) At short intervals (5 to 15 minutes) after ferritin administration, the tracer was found at high concentration in the lumen and endothelial fenestrae, and at decreasing concentrations embedded throughout the basement membrane and incorporated into the epithelium (within cytoplasmic vesicles and within invaginations of the plasmalemma facing the basement membrane). After longer intervals (1 to 3 hours) the distribution of the tracer within the capillary wall was similar except that its concentration in the epithelium was higher, and, in addition to plasma membrane invaginations and small vesicles, ferritin also marked larger vacuoles, dense bodies, and intermediate forms. Large accumulations of tracer typically occurred in the spongy areas of the basement membrane, especially in the axial regions. Ferritin also appeared in the endothelium within membrane-limited vacuoles and dense bodies, particularly in the deep cells. After 6 to 44 hours the tracer still occurred in the lumen and throughout the basement membrane. The ferritin deposits in the spongy areas as well as the ferritin-containing vacuoles of the deep endothelium were larger and more numerous. In the epithelium ferritin was found not only within various membrane-limited bodies, but also "free" within the cytoplasmic matrix. These observations indicate that in the nephrotic glomerulus, as in the normal, the basement membrane functions as the main filtration barrier; however, in nephrosis, the basement membrane is defective and allows leakage of increased quantitites of ferritin and presumably plasma proteins. The basement membrane defect appears to be fine and widespread, occurring at or near the molecular level of organization of the filter. The accumulation of unfiltered ferritin in axial regions together with the demonstration of its subsequent phagocytosis by the "deep" endothelial cells suggest that the latter may function in the removal of filtration residues. Finally, the findings indicate that in the nephrotic, as in the normal animal, the epithelium acts as a monitor that recovers, at least in part, the protein which leaks through the filter, and that in nephrosis, the recovering activities of the epithelium are greatly enhanced because of the increased permeability of the basement membrane.

scholarly journals GLOMERULAR PERMEABILITY

1961 ◽  
Vol 113 (1) ◽  
pp. 47-66 ◽  
Author(s):  
Marilyn G. Farquhar ◽  
Steven L. Wissig ◽  
George E. Palade
Keyword(s):  
Basement Membrane ◽  
Kidney Tissue ◽  
Structural Features ◽  
Capillary Wall ◽  
High Concentration ◽  
Glomerular Permeability ◽  
Glomerular Capillary Wall ◽  
Glomerular Capillary ◽  
Filtration Barrier ◽  
Visceral Epithelium

Ferritin was used as a tracer to investigate pathways and mechanisms for transfer across the various layers of the glomerular capillary wall. Kidney tissue, fixed at intervals of 2 minutes to 2 hours following an intravenous injection of ferritin, was examined by electron microscopy. The observations confirmed the existence of three distinct and successive layers in the glomerular capillary wall (the endothelium, the basement membrane, and the visceral epithelium). In addition, they demonstrated a number of new structural features: namely (a) discrete fibrils in the subendothelial spaces; (b) a characteristic, highly elaborate, cytoplasmic organization in the visceral epithelium; and (c) special structures resembling "desmosomes" in the slits between foot processes. In animals sacrificed at short time intervals (2 to 15 minutes) following ferritin administration, ferritin molecules were found at high concentration in the lumen and endothelial fenestrae, at low concentration in the basement membrane, and in very small numbers within the epithelium. Later (1 to 2 hours), the tracer particles were still present in the lumen and within endothelial fenestrae, and, in addition, had accumulated on the luminal side of the basement membrane, especially in the axial regions of the vessels. Larger numbers of ferritin molecules were also found in the epithelium—in invaginations of the cell membrane at the base of the foot processes, and in various membrane-limited bodies (vesicles, multivesicular bodies, vacuoles, and dense bodies) present within the cytoplasm. These observations suggest that the endothelial fenestrae are patent and that the basement membrane is the main filtration barrier. Since the basement membrane has no demonstrable pores, it is probably not a simple sieve but presumably is a gel-like structure with two fine fibrillar components embedded in an amorphous matrix. Both the epithelium and endothelium may be concerned with building and maintaining this structure. Finally, the intracellular accumulation of particles in the epithelium suggests that the latter acts as a monitor that recovers, at least in part, the small amounts of protein which normally leak through the filter.

Albumin-Induced Endocytic Vacuoles in Tetrahymena Pyrijormis

1975 ◽  
Vol 33 ◽  
pp. 694-695
Author(s):  
L. J. Brenner ◽  
D. G. Osborne ◽  
B. L. Schumaker
Keyword(s):  
Electron Microscopy ◽  
Bovine Serum Albumin ◽  
Bovine Serum ◽  
Protein Concentration ◽  
Tetrahymena Pyriformis ◽  
Sequence Of Events ◽  
Cytoplasmic Bodies ◽  
Food Vacuoles ◽  
Mouse Ascites ◽  
Normal Human

Exposure of the ciliate, Tetrahymena pyriformis, strain WH6, to normal human or rabbit sera or mouse ascites fluids induces the formation of large cytoplasmic bodies. By electron microscopy these (LB) are observed to be membrane-bounded structures, generally spherical and varying in size (Fig. 1), which do not resemble the food vacuoles of cells grown in proteinaceous broth. The possibility exists that the large bodies represent endocytic vacuoles containing material concentrated from the highly nutritive proteins and lipoproteins of the sera or ascites fluids. Tetrahymena mixed with bovine serum albumin or ovalbumin solutions having about the same protein concentration (7g/100 ml) as serum form endocytic vacuoles which bear little resemblance to the serum-induced LB. The albumin-induced structures (Fig. 2) are irregular in shape, rarely spherical, and have contents which vary in density and consistency. In this paper an attempt is made to formulate the sequence of events which might occur in the formation of the albumin-induced vacuoles.

Structural determinants of glomerular hydraulic permeability

1994 ◽  
Vol 266 (1) ◽  
pp. F1-F12 ◽  
Author(s):  
M. C. Drumond ◽  
W. M. Deen
Keyword(s):  
Basement Membrane ◽  
Hydraulic Resistance ◽  
Structural Changes ◽  
Water Movement ◽  
Capillary Wall ◽  
Hydraulic Permeability ◽  
Structural Determinants ◽  
Membrane Area

To elucidate which structures determine the resistance to water movement, we used a computational fluid dynamics approach to determine velocity and pressure fields within the glomerular capillary wall. The model included representations of the endothelial fenestrae, basement membrane, and epithelial filtration slits with slit diaphragms. The input data included dimensions of the various structures from previous electron microscopy studies, as well as the hydraulic permeability recently measured for isolated films of glomerular basement membrane in vitro. The hydraulic resistance of the endothelium was predicted to be small, whereas the basement membrane and filtration slits were each found to contribute roughly one-half of the total hydraulic resistance of the capillary wall. It was calculated that, for a given filtrate flux, the pressure drop within basement membrane in vivo is roughly twice that of “bare” or isolated basement membrane, because of the small fraction of basement membrane area exposed. The dominant resistance in the filtration slit was found to be the slit diaphragm. Predicted values for the overall hydraulic permeability of the capillary wall were within the experimental range derived from micropuncture measurements in normal rats. The model should be a useful tool for analyzing the effects of various structural changes on glomerular hydraulic permeability. This is illustrated by applying the model to recent physiological and morphometric data in nephrotic rats.

scholarly journals Maturation of the developing renal glomerulus with respect to basement membrane proteoglycans

1987 ◽  
Vol 32 (4) ◽  
pp. 498-506 ◽  
Author(s):  
Brigitte Lelongt ◽  
Hirofumi Makino ◽  
Yashpal S. Kanwar
Keyword(s):  
Basement Membrane ◽  
Renal Glomerulus

scholarly journals Effects of experimental nephrosis on basement-membrane components and enzymes of collagen biosynthesis in rat kidney

1985 ◽  
Vol 226 (1) ◽  
pp. 243-250 ◽  
Author(s):  
A Jukkola ◽  
J Risteli ◽  
H Autio-Harmainen ◽  
L Risteli
Keyword(s):  
Membrane Proteins ◽  
Basement Membrane ◽  
Indirect Immunofluorescence ◽  
Type Iv Collagen ◽  
Rat Kidney ◽  
Kidney Tissue ◽  
Kidney Cortex ◽  
Collagen Biosynthesis ◽  
Type Iv ◽  
Basement Membrane Proteins

The aim of the present study was to find out whether the basement-membrane proteins laminin and type IV collagen are involved in the development of aminonucleoside-induced nephrosis. These proteins were measured by specific radioimmunoassays in serum, urine and kidney-cortex samples, and they were localized in the glomeruli by indirect immunofluorescence. Nephrosis was induced in rats with a single intraperitoneal injection of puromycin aminonucleoside. Serum laminin concentrations, detected by a radioimmunoassay for the P2 domain of the protein, increased to reach a maximum at days 5-7, and they remained elevated until at least day 14. The increase preceded the development of proteinuria, suggesting a role for laminin in glomerular function. Concomitant with proteinuria, increasing amounts of laminin antigenicity were also found in the urine. The size of the laminin antigen in serum was estimated by gel filtration, and the serum forms were found to contain both the P1 and the P2 regions of the intact laminin molecule. On the other hand, there were no changes in the serum or urinary concentrations of type-IV-collagen-derived antigens, as detected by a radioimmunoassay for the 7S collagen domain of this protein. The total content of laminin in kidney cortex, measured after digestion of the tissue with trypsin and collagenase, was, at day 9, still comparable with normal values, and the distribution of both basement-membrane proteins in the glomeruli, studied by indirect immunofluorescence, was similar to that in the controls. The tissue damage induced by aminonucleoside, however, seems to stimulate collagen biosynthesis, as the activities of prolyl 4-hydroxylase, lysyl hydroxylase and galactosylhydroxylysyl glucosyltransferase in kidney tissue increased significantly, with maxima at days 8-10.

Cellular and extracellular involvement in the regeneration of the rat lower vibrissa follicle

Development ◽  
1992 ◽  
Vol 114 (4) ◽  
pp. 887-897 ◽  
Author(s):  
C.A. Jahoda ◽  
K.A. Horne ◽  
A. Mauger ◽  
S. Bard ◽  
P. Sengel
Keyword(s):  
Basement Membrane ◽  
Hair Follicle ◽  
Wound Repair ◽  
Type Iv Collagen ◽  
Initial Response ◽  
Type Iv ◽  
Sequence Of Events ◽  
Papilla Formation ◽  
Wound Reaction ◽  
Dermal Cells

The sequence of events leading to the reconstruction of a fibre-producing hair follicle, after microsurgical amputation of the lower follicle bulb, has been detailed by immunohistology and electron microscopy. The initial response was essentially found to be a wound reaction, in that hyperproliferative follicle epidermis quickly spread to below the level of amputation—associated with downward movement of mesenchymal (or dermal) sheath cells. Fibronectin was prominent in both dermis and epidermis at this stage and, as in wound repair, preceded laminin and type IV collagen in covering the lower dermal-epidermal junction. Once a new basal line of epidermis and a complete basement membrane were established, laminin and type IV collagen were detected below this junction and within the prospective papilla-forming mesenchyme. This coincided with ultrastructural observations of profuse sub-basement membrane extracellular material in the region of new papilla formation. The glassy membrane displayed extensive ultrastructural modifications at its lower level, and these corresponded with localized variations in staining intensities for all three antibodies over time. The membrane hung below the level of the epidermis, and was crossed by migrating cells from the mesenchymal dermal sheath of the follicle - it acted to segregate the inner group of follicular dermal cells from wound fibroblasts. Extracellular matrix may be a mediator of the dermal-epidermal interactions associated with this hair follicle regeneration phenomenon.

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