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M Elger

Publications and source records attributed to M Elger.

At least 37 records · Page 2Linked to original sources

A role for podocytes to counteract capillary wall distension.

In a previous study of the changes in glomerular structure in the isolated perfused kidney (IPK), perfusion at high pressures lead to an enlargement of the glomerular tuft and to the formation of giant capillaries. The present paper analyzes the morphological and dimensional changes of the peripheral glomerular capillary wall under these circumstances. The enlargement of glomerular capillaries at high pressure perfusion was accompanied by a considerable increase in the surface area of the glomerular basement membrane (GBM). The podocyte as well as the endothelial layer perfectly adapted to the acute challenge in covering increasing GBM area. The interdigitating foot process pattern showed up in an ideal arrangement. The capillary wall expansion was associated with a significant increase in total pericapillary slit area. Compared to the corresponding low pressure groups (65 mm Hg, without and with the application of vasodilators) the slit area increased in the high pressure groups (105 mm Hg, without and with vasodilator) by approximately 50 and 75%, respectively. This increase of the slit area was mainly due to an increase in slit length; the slit width remained fairly constant. These findings indicate that the pericapillary wall is distensible based on a distensibility of the GBM. We suggest that the contractile apparatus of podocyte foot processes regulates the expansion of the GBM.

Animals↗

Renal tubule of dogfish, Scyliorhinus caniculus: a comprehensive study of structure with emphasis on intramembrane particles and immunoreactivity for H(+)-K(+)-adenosine triphosphatase.

The ultrastructure of renal tubule cells was studied in the European lesser spotted dogfish by the evaluation of thin sections and freeze fracture replicas. Computer-assisted three-dimensional reconstruction of entire nephrons was performed. The distinction of nephron segments and collecting tubule was made using results of previous histological work. The first proximal tubule segment (PI) consists of two subsequent portions, PIa and PIb. PIa is a component of the lateral countercurrent bundle, and PIb, which displays an apical tubulovesicular apparatus and an extended lysosomal compartment, is located in the vicinity of the glomeruli. Rod-shaped intramembrane particles were detected in PIa. The second proximal tubule segment (PII) is a special segment in elasmobranch and teleost fish. PII differs largely from PI in cell morphology and function. The apical cytoplasm was filled with small clear vesicles, and an apical endocytic apparatus was lacking. In the apical cell membrane, rod-shaped particles were revealed by freeze fracture. The apical tight junctions of PI and PII consisted of seven to ten meandering strands. The distal nephron was subdivided into two major segments: early distal tubule (EDT) in the lateral countercurrent bundles and late distal tubule (LDT) in the mesial tissue. The EDT showed marked amplification of basolateral cell membranes. The tight junctions displayed a low number of continuous parallel strands, which is also characteristically found in the diluting segments of other vertebrates. LDT cells showed cytoplasmic studs and rod-shaped intramembraneous particles at the apical cell membrane, thereby resembling type A intercalated cells of collecting duct. The collecting tubule (CT) emerged from the LDT and was part of the countercurrent arrangement inside the lateral bundles. Tight junctions of LDT and CT consisted of many meandering strands in a honeycomb pattern. With immunohistochemistry, binding sites of a polyclonal antibody against an extraplasmic portion of rat gastric H(+)-K(+)-adenosine triphosphatase (ATPase) were observed at the apical cell membrane of PIa, PII, and LDT. From the colocalization of binding sites for the antibody against the transport enzyme with rod-shaped intramembrane particles, we assume that these might be the morphological correlate of gastric H(+)-K(+)-ATPase-like enzyme in the renal tubule.

Animals↗

Cultured rat mesangial cells contain smooth muscle alpha-actin not found in vivo.

A monoclonal antibody against smooth muscle alpha-actin (SM alpha-actin) was used to study the expression of SM alpha-actin in kidney sections and mesangial cell (MC) cultures. In the tissue sections, indirect immunofluorescence revealed intense labeling of vascular smooth muscle cells and precapillary pericytes for SM alpha-actin. Glomerular cells including MC were negative, with the exception of scattered smooth muscle cells in the wall of the intraglomerular segment of the efferent arteriole. In contrast, in MC cultures 50 to 95% of the cells displayed bright fluorescence. Immunoreactivity for SM alpha-actin first appeared 3 days after explanation of glomeruli and increased until the primary culture reached subconfluence. In each subculture (1 to 10) expression of SM alpha-actin was weak on day 1 and pronounced at subconfluence. Growth arrest of subconfluent cultures for 1 to 7 days in serum-free medium did not alter the percentage of cells positive for SM alpha-actin. However, exposure of MC to serum-free medium beginning on the first day of subculture curtailed expression of SM alpha-actin. Double-labeling with antibodies against proliferating cell nuclear antigen and SM alpha-actin revealed SM alpha-actin-positive filaments in both replicating and resting cells. In summary, our results demonstrate that some process or processes associated with cell proliferation and cell growth of MC are accompanied by de novo expression of SM alpha-actin. The relevance to the contractile behavior of the difference in SM alpha-actin expression under in vitro and in vivo conditions is unknown.

Actins↗

The glomerular mesangium: capillary support function and its failure under experimental conditions.

We present a structural analysis of the ability of the biomechanical unit consisting of mesangium and glomerular basement membrane to maintain normal capillary architecture in the face of mechanical challenges due to high intraglomerular pressures. Capillary support function may be considered in terms of the stabilization of local form (development of wall tension against capillary dilation) and global form (centripetal fixation of capillary loops to maintain higher order form). The pathologic consequences of the loss of this support are illustrated by way of experimental models of mechanical mesangial failure. Such failure may express itself as mesangial widening, increased transmesangial macromolecule "traffic," ballooning of capillary segments, and unfolding of capillary loops. Mechanisms are described by which these structural changes may lead to segmental glomerular sclerosis.

Animals↗

Morphometric analysis of kidney hypertrophy in rats after chronic potassium depletion.

Hypertrophic kidney growth in K depletion was analyzed morphometrically in rats fed a K-free diet for 18 days. K excretion decreased rapidly to less than 1% of control, creatinine clearance decreased, and urinary concentrating ability was impaired. Kidney weight in K-depleted rats was 30% higher than in controls. Growth of individual kidney zones was not uniform; hypertrophy of the inner stripe (IS) of the outer medulla was most prominent. Among tubules the most striking enlargement was seen in the outer medullary collecting duct (CD); hypertrophy and hyperplasia of both CD cells and intercalated (IC) cells occurred in the same proportion. In the IS, both luminal and basolateral membrane area per unit tubule length doubled in IC cells and increased 1.2- and 1.7-fold, respectively, in CD cells. Despite overall kidney growth, epithelial volume of thick ascending limb (TAL) per tubule length was unchanged in IS and cortex and only slightly increased in outer stripe. The increased membrane area of CD epithelium in the IS is consistent with previously reported increases in activity of enzymes involved in active reabsorption of K+ and Na+.

Animals↗

Branching and confluence pattern of glomerular arterioles in the rat.

In addition to the usual division of the glomerular tuft into lobules, a subdivision into an afferent and an efferent capillary domain is made. Immediately after entering the glomerulus the afferent arteriole splits into superficially located branches which supply the lobules. The capillaries of each lobule first run towards the urinary pole; these parts of each lobule establish the afferent domain. The capillaries of each lobule running back towards the vascular pole establish the efferent domain. The afferent domain represents the major part of the tuft; it has the shape of an incomplete globe with a deep depression on one side within which the efferent domain is situated. The efferent arteriole is established inside the glomerular tuft within the efferent capillary domain. Generally tributaries from each lobule converge to form the intraglomerular segment of the efferent arteriole, which leaves the tuft by passing through the mesangium of the glomerular stalk. At this site the intraglomerular segment of the efferent arteriole is fully surrounded by the mesangium; consequently, it is exposed to the intramesangial pressure.

Animals↗

Role of mesangial cell contraction in adaptation of the glomerular tuft to changes in extracellular volume.

Different chronic states of mesangial cell contraction were induced by variation of extracellular volume in Munich-Wistar rats for 6 days to study the influence of mesangial cells on the geometry of the glomerular tuft. Stereological analysis of superficial glomeruli in volume-expanded rats (VE, treated with enalapril) and volume-reduced rats (VR, treated with indomethacin) revealed a glomerular tuft volume 28.7% smaller, and a capillary luminal volume 32% smaller in VR than in VE rats. The filtration area [defined as glomerular basement membrane (GBM) area facing fenestrated endothelium] was greatly reduced in VR rats (97 +/- 16 X 10(3) micron 2 vs 137 +/- 13 x 10(3) micron 2). The surface density (Sv) of the GBM was higher by approximately 10% in VR rats primarily due to the considerable increase in Sv of the perimesangial GBM subdivision (0.189 +/- 0.01 micron 2/micron 3 vs 0.153 +/- 0.01 micron 2/micron 3), indicating a higher degree of mesangial cell contraction in these animals. Our results suggest (1) that mesangial cell contraction plays a major role in the adaptation of the glomerular tuft to variations in extracellular volume; (2) that the relevance of mesangial cell contraction for the regulation of glomerular haemodynamics appears to be small; and (3) that the reduction in filtration area, although prominent, cannot fully account for the considerable decreases in the ultrafiltration coefficient observed by others in acute and chronic studies.

Adaptation, Physiological↗

Mesangial cell-glomerular basement membrane connections counteract glomerular capillary and mesangium expansion.

Glomerular capillaries are perfused at a high hydraulic pressure. Since the capillary mesangium interface presents no morphologically apparent pressure barrier, it is suggested that the hydraulic pressure in the mesangium may also be high. This paper analyzes the structures in the glomerular tuft that are capable of counteracting the distending forces exerted on the tuft by the high hydraulic pressure in its center. The skeletal element of the glomerular tuft is the glomerular basement membrane (GBM). The combination of the GBM with the contractile apparatus of mesangial cells represents the main system stabilizing the glomerular tuft. The mesangial cell-GBM connections counteracting the expansion of glomerular capillaries appear less susceptible to injury than those counteracting mesangial expansion.

Animals↗

Structure of the glomerular mesangium: a biomechanical interpretation.

This paper summarizes our current knowledge of the structural details and probable functional significance of the system of contractile filaments in the glomerular mesangium. The description is based mainly on studies of superficial glomeruli of the rat kidney. The contractile apparatus of mesangial cells consists of microfilament bundles located predominantly within mesangial cell processes. The thickest microfilament bundles occur in the juxtacapillary mesangial cell processes, which directly abut the glomerular capillaries. The effector structure of mesangial cell contractility is the GBM. Mesangial cell processes are connected to the GBM either directly or through the interposition of extracellular microfibrils. In general, the contractile system of the mesangium interconnects opposing parts of the GBM. This arrangement is particularly obvious in the juxtacapillary processes, which underlie a mechanical connection between the GBM at the two opposing mesangial angles of a single capillary. The geometry and structural composition of the contractile apparatus of the mesangium indeed suggest a static rather than a dynamic function. In conjunction with the GBM, the mesangial contractile apparatus seems capable of supporting sufficient wall tension to counteract the distending forces acting across the capillary walls; the apparatus also seems capable of directly balancing the distending forces on the perimesangial walls. Assuming that mesangial cells are capable of isotonic contractions, the effect of such a contraction on capillary diameter and, consequently, on filtration area would be small.

Actin Cytoskeleton↗

Microfibrils are a major component of the mesangial matrix in the glomerulus of the rat kidney.

The mesangial matrix of the rat glomerulus was studied by transmission electron microscopy in specimens preserved by a modified technique, which avoids osmium tetroxide but uses tannic acid as a contrasting agent. It can be demonstrated that microfibrils are a major component of the normal glomerular mesangial matrix. They are non-branching tubular structures with a hollow centre, an undefined length and a thickness of approximately 15 nm. Microfibrils make up a dense fibrillar network interconnecting mesangial cells and glomerular basement membrane.

Animals↗

The ultrastructural organization of the basement membrane of Bowman's capsule in the rat renal corpuscle.

The basement membrane of Bowman's capsule (BCBM) of the rat was studied by means of a modified tissue-preservation technique for transmission electron microscopy, which avoids the usual thorough fixation in OsO4 and applies tannic acid and uranyl acetate for staining (Sakai et al. 1986). At most sites the BCBM is multilayered, consisting of one to seven dense layers separated by electron-lucent layers. The latter, which can be termed laminae rarae, contain fine filaments which connect the dense layers to each other and the innermost dense layer to the basal cell membrane of the parietal epithelium. The laminae densae are basically composed of fine filaments arranged in an anastomosing pattern. Individual filaments ranging from 5 to 15 nm in diameter, combine to form filament bundles up to 100 nm in thickness and 1 to 2 micron in length. Within a dense layer, filaments and filamentous bundles are oriented mainly in the same direction. Often the inner dense layers do not form a continuous sheet, and the filamentous bundles are arranged in anastomosing or spiral patterns to form a ribbon-like structure that we call a "microligament". These microligaments are often embedded in basal furrows of the parietal epithelium and are best developed around the vascular pole. Intracellular actin bundles of the parietal cells are regularly associated with these extracellular ribbon-like structures of the basement membrane. In conclusion, the BCBM has an unusual structure: the laminae densae are characterized by their filamentous nature and are arranged in different patterns, i.e. as a multilayered mat and as microligaments.

Animals↗