Advances in the cellular mechanisms of secretory component synthesis and secretion and the transport of IgA.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
W R Brown
Publications and source records attributed to W R Brown.
[Localization of Ulex europaeus agglutinin-1 (UEA1) binding sites in normal and 1,2-dimethylhydrazine (DMH) treated rat bowel].
Explore the source record for details and available documents.
1,2-Dimethylhydrazine↗
Studies of the action spectrum for induction of photosensitivity to tetrachlorosalicylanilide in mice.
We have developed a new system, using ear swelling in mice, to study the action spectrum for the induction of photosensitivity to tetrachlorosalicylanilide (TCSA). Using narrow-band interference filters, we produced data for action spectra between 250 nm and 421 nm with doses of 0.5 J/cm2 and 0.2 J/cm2. We found that the higher dose generally produced greater reactions. The action spectrum was similar to the absorption spectrum for TCSA in the UVA region. The reduced responses in the UVB and UVC regions may be due to immunological suppression produced by these parts of the spectrum.
Animals↗
Specific antibodies to cholera toxin in rabbit milk are protective against Vibrio cholerae-induced intestinal secretion.
Breast feeding helps to protect the nursing infant against infectious diarrhoeas, but the relative importance of antibodies compared with other components present in milk is unsettled. In order to aid in resolving this issue we evaluated the ability of milk, collected from rabbits not immunized or immunized enterally during pregnancy with toxinogenic, live Vibrio cholerae, to inhibit water secretion induced by V. cholerae in rat ileal loops. Non-immune milk was not inhibitory, whereas immune milk was. The inhibitory component of the immune milk was immunoglobulin by virtue of its molecular weight and absorption by an anti-rat immunoglobulin immunosorbent. In addition, the inhibitory antibodies were principally antibodies to cholera toxin because they could be removed from the milk by a cholera toxin immunosorbent but were only partially removed by incubation with whole V. cholerae. Thus, in rabbit milk, we could implicate specific antibodies in protection against intestinal water secretion induced by V. cholerae.
Animals↗
Intestinal uptake of IgG in suckling rats. Distinction between jejunal and ileal epithelial cells demonstrated by simultaneous ultrastructural localization of IgG and acid phosphatase.
During the suckling period, the proximal small intestine of neonatal rats absorbs maternal milk immunoglobulin G (IgG) into the circulation by a receptor-mediated mechanism. At the same time, milk IgG enters vacuoles in the distal small intestine unaided by a receptor and is degraded. To help define the distinction between the handling of IgG by the proximal and distal neonatal small intestine, we simultaneously localized IgG (by peroxidase-labeled antibodies) and acid phosphatase (by a lead phosphate technique) at the ultrastructural level. In the proximal small intestinal epithelial cells, IgG-containing vesicles were separate from acid phosphatase-containing structures, whereas in the distal intestinal epithelial cells, IgG was present together with acid phosphatase in large supranuclear vacuoles. These observations are consistent with the hypothesis that IgG avoids degradation in the proximal intestinal cells because vesicles in which it is transported do not fuse with lysosomes, whereas IgG in the distal small intestine is degraded in lysosomal enzyme-containing organelles.
Acid Phosphatase↗
Uniform epidermal cell proliferation in the mouse tympanic membrane.
Autoradiographic studies in mice showed epidermal cell proliferation to be dispersed over the whole tympanic membrane with no specific proliferative center. This strengthens the concept that net migration of the superficial layer of the stratum corneum across the tympanic membrane is the result of random insertion of cells into a pavement-like layer of corneocytes. We also found the cell proliferation rate in tympanic epidermis to be the same as that for dorsal epidermis in both normal mouse skin and the hyperproliferative epidermis of asebia mice. There was no indication of more rapid migration in tympanic epidermis in asebia as a result of the increased proliferation rate but rather increased thickness of the tympanic epidermis. There were also unusual circular mounds of epidermal cells in all asebia tympana, apparently due to localized hyperproliferation.
Animals↗
Effects of monensin on vesicular transport pathways in the perfused rat liver.
In the rat hepatocyte, the internalization and degradation of asialoglycoproteins and the secretion of plasma and biliary proteins require specific intracellular sorting of vesicles. To aid in the biochemical characterization of these different vesicular pathways, we examined the effects of the ionophore monensin on the uptake and degradation of 125I-asialoorosomucoid (ASOR) and on the secretion of plasma and biliary proteins by the in situ perfused rat liver. In control livers, 77% of injected 125I-ASOR was extracted on first pass; 93% of the extracted radioactivity was released back into the circulation (totally degraded and some intact ASOR was found); and approximately 2% was recovered in the bile, some of which was intact. Monensin treatment decreased first pass uptake of 125I-ASOR to 57% and abruptly blocked the release of radioactivity into the perfusate and the bile. When hepatic proteins were biosynthetically labeled with 3H-leucine, monensin treatment dramatically reduced and delayed the secretion of newly synthesized proteins into both the perfusate and the bile. In contrast with control livers, in which secretion of protein into the perfusate preceded secretion of protein into the bile, TCA-precipitable 3H-protein appeared in bile about 20 min before TCA-precipitable 3H-protein appeared in the perfusate in monensin-treated livers. Thus, monensin treatment in the perfused liver blocked the degradation of asialoglycoproteins and inhibited the secretion of plasma proteins but had less effect on biliary protein secretion. These data document physiologic effects of monensin in an intact organ and suggest that biochemical distinctions between different vesicular pathways exist in the rat hepatocyte.
Animals↗
Macrophages in the interstitial tissue of the rat testis.
Macrophages were identified in the intertubular tissue of the rat testis by loading animals with a particulate vital dye (trypan blue or India ink) and by localizing immunocytochemically a macrophage membrane antigen (MRC W3/25). Leydig cells were identified by the histochemical staining reaction for 3 beta-hydroxysteroid dehydrogenase activity and by a monoclonal antibody. Macrophages were scattered in the interstitial tissue closely attached to and mixed with the Leydig cells. They were never found in the seminiferous tubules. The macrophages comprised about 25% of all the cells in the interstitium. Double staining with a vital dye and a marker antibody showed that all the phagocytosing cells were macrophages and that the Leydig cells did not take up vital dyes. Double staining for the demonstration of the 3 beta-hydroxysteroid dehydrogenase activity and the macrophage antigen likewise revealed two distinctly different cell populations. Crude Leydig cell preparations obtained by collagenase treatment of the testis contained macrophages (12-14%). Macrophages were present throughout the postnatal prepuberal development of the testis. Their density was increased in the cryptorchid and irradiated testis.
3-Hydroxysteroid Dehydrogenases↗
Immunocytochemical localization of sphingolipid activator protein-1, the sulfatide/GM1 ganglioside activator, to lysosomes in human liver and colon.
Sphingolipid activator proteins (SAP) stimulate the enzymatic hydrolysis of sphingolipids. The results of biochemical studies have suggested that SAP are located within lysosomes. In this study we sought immunocytochemical verification of the lysosomal location of SAP-1, a SAP that stimulates the hydrolysis of sulfatide and GM1 ganglioside. We stained adjacent sections of normal adult liver and colon for either SAP-1, by peroxidase-labeled antibodies, or acid phosphatase, by enzyme histochemistry. At the light microscopic level, SAP-1 and acid phosphatase were present in similar cells of the colonic lamina propria and hepatic sinusoids, and in similar supranuclear sites of colonic epithelial cells. By electron microscopy, SAP-1 was present in vesicular structures morphologically similar to those containing acid phosphatase. Thus, SAP-1 is present in lysosomes of several different kinds of cells in the normal human liver and colon.
Adult↗
Dietary fat alters progression of some age-related changes of the immune system.
SJL mice develop resistance against tolerance between the 9th and 25th wk of life. This resistance is linked with a loss of suppressor capacity in the thymus. We have shown here that contact photosensitivity (CPS) decreases as a function of age and that this is due to an age-dependent increase in suppressor capacity. Diet fats have a differential effect on age-dependent changes in suppressor activity; a low P/S diet prevents or delays loss of suppressor activity for antibody formation and a high P/S diet prevents or delays the development of suppressor activity in CPS reactions.
Aging↗
Silicosis in barium miners.
Four men who mined barytes in Scotland and who developed pneumoconiosis are described. Three developed progressive massive fibrosis, from which two died; and one developed a nodular simple pneumoconiosis after leaving the industry. The radiological and pathological features of the men's lungs were those of silicosis and high proportions of quartz were found in two of them post mortem. The quartz was inhaled from rocks associated with the barytes in the mines. The features of silicosis in barium miners are contrasted with the benign pneumoconiosis, baritosis, that occurs in workers exposed to crushed and ground insoluble barium salts. Diagnostic difficulties arise when silicosis develops in workers mining minerals known to cause a separate and benign pneumoconiosis. These difficulties are compounded when, as not infrequently happens, the silicotic lesions develop or progress after exposure to quartz has ceased.
Aged↗
Dose response studies for UVA in contact photosensitivity to TCSA in the mouse.
We performed UVA dose response studies for contact photosensitivity (CPS) to 3,3',4',5-tetrachlorosalicylanilide (TCSA) in BALB/cJ mice using the back for induction and the ears for elicitation. The dose of TCSA was kept constant. The challenge procedure in non-sensitized mice produced a phototoxic response at 24 h after challenge. None of the 11 mice tested showed simple contact sensitivity (CS) to TCSA. Vigorous CPS responses were achieved with sensitization doses of UVA as low as 0.5 J/cm2 and the peak reaction occurred at 24 h after challenge. UVA sensitization doses less than 0.5 J/cm2 gave responses that were reduced in a dose-related manner and the peak response was delayed to 48 h or longer after challenge. The maximum elicitation dose of 6.0 J/cm2 UVA gave the greatest response and almost all ears showed vigorous reactions if the sensitization dose was 0.5 J/cm2 or greater. Lower elicitation doses gave lesser reactions in a dose-related manner. Cyclophosphamide (Cy) pretreatment increased the CPS reaction by about 50%.
Animals↗
The duration of contact photosensitivity to TCSA in the mouse.
We examined the course and duration of contact photosensitivity (CPS) to 3,3', 4',5-tetrachlorosalicylanilide (TCSA) in BALB/cJ mice. The doses of TCSA and UVA at sensitization and challenge were kept constant and the time between sensitization and challenge was varied between 4 days and 9 weeks. A small increase in ear swelling was seen at the 4-d challenge with a further increase at 5 d. The peak challenge response was reached at 7 d. Gradually decreased reactions were found at challenges 2,3 and 5 wk after sensitization and, at 7 and 9 wk challenges, sensitization was not detected. Resensitization of the 9-wk group, with challenge a week later, produced a good reaction though not a maximum one, thus the waning of sensitization was not due solely to active suppression.
Animals↗
Secretory component: the polymeric immunoglobulin receptor. What's in it for the gastroenterologist and hepatologist?
The primary function of the SC-pIg system is to secrete pIgs into various external secretions. The cellular mechanism responsible for this transport is schematically depicted in Figure 5. Polymeric immunoglobulin A, which is synthesized by plasma cells that are part of the mucosa-associated lymphoid tissue, gains access to the SC on the abluminal surface of epithelial cells by diffusion from sites of synthesis in mucosae or enters the blood circulation and is cleared, largely by hepatic transport, into bile. The pIgA binds to SC on the abluminal surface of the epithelial cells (and probably hepatocytes) initially by noncovalent interactions that are saturable, reversible, and specific for pIgA and IgM. Subsequently, covalent interaction between SC and its ligand occurs to a variable degree in different species. The SC-IgA complex is endocytosed by the epithelial cell or hepatocyte and is transported across the cell into the external secretions by a microtubule-dependent vesicular transport mechanism. At some point during the transport, the complex is rendered soluble by proteolytic cleavage of the membrane-associated SC molecule to release the soluble sIgA into the gland lumen or the canaliculus. In the intestinal lumen, SC helps protect the sIgA molecule from proteolytic degradation. The sIgA may play a major role in the mucosal defense against pathogenic organisms or harmful antigens. The SC-pIg system differs from many of the other known receptor-ligand interactions in several important ways. First, the synthesis or expression of the receptor (SC), or both, are not regulated by the concentration of the ligand. Second, SC probably is not dissociated from its ligand or recycled to the cell surface as it is secreted in complex with its ligand (pIg) into the external secretions. Third, the interaction of pIgs with their receptor does not function to regulate an intracellular process, but results in transcellular transport of the ligand, which acts in the external environment. Fourth, after initial noncovalent, reversible binding between the receptor and its ligand, the interaction becomes covalent by the formation of disulfide linkages between SC and the pIg. Finally, SC is initially inserted into the abluminal domain of epithelial cells as an integral membrane protein and subsequently is proteolytically cleaved to a soluble molecule which is secreted by the cell. Thus, in contrast to many cell-surface receptor-ligand interactions in which the ligand is ultimately degraded and the receptor is conserved, the SC-pIgA interaction results in partial proteolytic degradation of the receptor and conservation of the ligand.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Epidermal growth in the bottlenose dolphin, Tursiops truncatus.
Epidermal growth in two mature female bottlenose dolphins, Tursiops truncatus, was investigated by following the movement of a cohort of tritiated thymidine-labeled epidermal cells for 59 days. The majority of the cells migrated in a cluster which was estimated to reach the skin surface in 73 days. We calculate that the outermost cell layer is sloughed 12 times per day. Turnover time and sloughing rate are estimated to be 1.7 times longer and 8.5 times faster than the respective values for epidermal cell kinetics in humans. This apparent inconsistency of slow transit time and rapid sloughing rate is reconciled by the convoluted structure of the stratum germinativum in the dolphin which results in a ratio of germinatival to superficial cells of 876:1. The stratum germinativum of dolphin epidermis appears to lack morphologically distinct, spatially segregated subpopulations of anchoring and stem cells. Dolphin epidermis has a large capacity for cell population, relatively long turnover time, and rapid sloughing rate. The adaptive advantages of these characteristics are discussed.
Animals↗
Hepatic uptake and disposition of human polymeric IgA1 in perfused rat liver: evidence for incomplete biliary excretion and intrahepatic degradation.
The hepatic uptake of polymeric immunoglobulin A (IgA) is mediated by secretory component; the resulting secretory IgA is excreted intact into bile. To define the hepatic metabolism of polymeric IgA, we quantitated the uptake and transport of human polymeric IgA1 after a single pass through the perfused rat liver. Uptake of polymeric IgA1 was compared with that of asialoorosomucoid, a glycoprotein whose uptake is mediated by the asialoglycoprotein receptor. Single-pass hepatic uptake of 125I-polymeric IgA1 and of 125I-asialoorosomucoid averaged 18.0 +/- 3.1% (SE) and 71.8 +/- 2.8%, respectively. The uptake of 125I-polymeric IgA1 was inhibited by excess unlabeled polymeric IgA1 but not by asialoorosomucoid. Only 13.0 +/- 1.6% of the 125I-polymeric IgA1 extracted by the liver was excreted into bile, whereas three-fourths was released into the hepatic venous effluent in degraded form. Thus, both the uptake and biliary excretion of polymeric IgA1 by the rat liver are inefficient processes. Polymeric IgA1 follows two distinct pathways after uptake by the liver: a small proportion is excreted intact into bile, while the majority is degraded and released back into the circulation.
Animals↗
IgA antibodies in rat bile inhibit cholera toxin-induced secretion in ileal loops in situ.
The biological actions of IgA antibodies in bile are largely undefined. We therefore tested whether biliary IgA antibodies could specifically inhibit cholera enterotoxin (CT)-induced secretion in the rat ileum. Rats were immunized by CT given orally or by injection into Peyer's patches. Bile was collected by bile duct cannulation, and anti-CT antibodies in the bile were measured by ELISA. CT plus bile from either immunized or unimmunized rats, or CT plus anti-CT-containing bile which had been absorbed by a CT immunosorbent, were instilled into in situ ileal loops in unimmunized rats; CT alone, or buffer was instilled into other loops. The bile used from the immunized rats contained IgA, but neither IgG nor IgM, anti-CT antibodies. It was found that bile containing IgA anti-CT antibodies almost totally inhibited the secretory effect of CT, and this inhibition was abrogated by absorption of the IgA anti-CT antibodies. Thus, IgA antibodies to an enterotoxin, secreted into bile, are effective against the enterotoxin in the rat intestine in vivo.
Animals↗
The binding of human milk lactoferrin to immunoglobulin A.
It was recognized that in human milk some amounts of lactoferrin (LF) were naturally bound to secretory IgA (sIgA). Since not only secretory component (SC) but also LF was released from sIgA by disulfide bond cleavage, it is conceivable that LF is naturally bound to IgA as well as SC. An in vitro binding test to LF and IgA was performed and the binding was confirmed by the use of an IgA-Sepharose 4B affinity column.
Chromatography, Affinity↗