A lectin-like receptor on rat macrophage membranes: colloidal gold probes for detection, localization and description of biological function.
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Animals↗
Biomedical subjects
H Kolb
Publications and source records attributed to H Kolb.
Identification of a subtype of cone photoreceptor, likely to be blue sensitive, in the human retina.
A minor population of cone photoreceptors (called B-cones) can be distinguished from the major population (called R-cones) on morphological criteria as seen by light microscopy in foveal and peripheral human retina. The B-cones are characterized by a longer inner segment projecting into subretinal space, a larger-diameter inner segment, an increased staining intensity of the inner segment, and a different distribution relative to the R-cones in the cone mosaic. B-cones occur even in the foveolar center (3-5%) and rise to a maximum (15%) in the foveolar slope. They can also be identified in peripheral retina where they form 7-10% of the total cone population. The B-cone population follows the distribution profile postulated for the blue-sensitive system from histochemical studies on monkeys and from psychophysical studies on humans. The B-cones also share many of the same morphological features of the putative blue cones of the ground squirrel and monkey retinas. For these reasons we suggest that our B-cone group is the blue cone population of the human retina.
Fovea Centralis↗
Mouse models of insulin dependent diabetes: low-dose streptozocin-induced diabetes and nonobese diabetic (NOD) mice.
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Animals↗
Distribution and morphology of dopaminergic amacrine cells in the retina of the turtle (Pseudemys scripta elegans).
A light microscopical study of the cell types that stain by immunohistochemistry for the synthesizing enzyme for dopamine, tyrosine hydroxylase, has been performed on the retina of the turtle Pseudemys scripta elegans. The immunostain can be localized to a single morphological type of amacrine cell. The cells are like A28 cells of a Golgi classification. They have medium sized dendritic fields that range in diameter from 200 to 700 micron with eccentricity from the visual streak. The amacrines have a tri-stratified dendritic tree with tiers of fine, curved dendrites ramifying in strata S1, lower S2 and the S4/5 border of the inner plexiform layer. We, like others, can find no good evidence that these cells are interplexiform cells. The dopaminergic amacrine cells have a low frequency (approximately 1300-1500 total cells in 130 mm2 retina), with their highest density occurring in the visual streak (60 cells per mm2). The density profiles fall in elliptical isodensity rings from the visual streak towards the peripheral retina. At all points on the retina the dendritic fields maintain a constant coverage factor independent of eccentricity. A comparison of the dopaminergic amacrine cells in the turtle and other vertebrate retinae is made.
Animals↗
The distinction by light and electron microscopy of two types of cone containing colorless oil droplets in the retina of the turtle.
In turtle retina the spectral types of cones can be distinguished by the characteristic colors of their oil droplets. Blue cones until recently were thought to be identified by their colorless oil droplets. Now it has been shown that the cones containing colorless oil droplets can be subclassified into two types: one type in which the oil droplet fluoresces under ultraviolet stimulation and the other type in which it does not. We have attempted to recognize these two subclasses of cones with colorless oil droplets by the following anatomical techniques. (1) Light microscopy of fresh retina, (2) light microscopy of isolated cells in tissue culture and (3) light and electron microscopy of photoreceptors stained with horseradish peroxidase in whole-mount. The cone type with the colorless fluorescent oil droplet (FC cone) has an oil droplet size intermediate between those contained in the green single cones and the cone with the clear colorless oil droplet (CC cone); it typically has a short (15 microns long) oblique axon and it forms approximately 13% of the cones in the retina. The CC cone, on the other hand, is recognized by having the smallest oil droplet of all cone types which is nonfluorescent; it has a very long (30 microns long) oblique axon and forms 5% of the cones in the retina. We discuss the similarity of the FC cone morphology and distribution to blue cones in other vertebrate retinas.
Animals↗
Recognition of xenogeneic erythrocytes: the GalNAc/Gal-particle receptor of rat liver macrophages mediates or participates in recognition.
We studied mechanisms that mediate recognition of human erythrocytes (HRBC) and sheep erythrocytes (SRBC) by rat liver macrophages. We used an in vitro cell binding assay that allows spontaneous formation of cell contacts. Binding of HRBC to rat macrophages shows the following characteristics: inhibition studies with several monosaccharides and oligosaccharides yield complete inhibition of cell contacts with saccharides, which block the GalNAc/Gal-particle receptor on rat liver macrophages. We found the inhibition pattern: N-acetyl-D-galactosamine, lactose greater than D-galactose, D-fucose greater than L-fucose much greater than N-acetyl-D-glucosamine. Cell binding is dependent on the presence of calcium ions, but not influenced by heat-aggregated IgG or gangliosides. The inhibition pattern was the same after treatment of HRBC with neuraminidase. Therefore, binding of HRBC, as well as binding of neuraminidase-treated HRBC, is mediated by the GalNAc/Gal-particle receptor. Binding of SRBC is partly inhibited by galactose-related saccharides. Binding is also partly inhibited by heat-aggregated IgG, gangliosides, and L-fucose. Complete inhibition of cell contacts with SRBC is achieved by combination of all inhibitors. We therefore conclude that binding of SRBC is mediated by several different mechanisms, including the GalNAc/Gal-particle receptor. Binding of neuraminidase-treated SRBC, however, was found to be completely inhibited by saccharides, which block the GalNAc/Gal-particle receptor. We conclude that the GalNAc/Gal-particle receptor mediates or participates in recognition of non-self structures.
Animals↗
Diabetogenic action of streptozotocin: essential role of membrane permeability.
A single high dose of streptozotocin was found to cause a transient increase in islet capillary permeability 2-4 h after administration. Staining of areas of increased vascular permeability by Evans blue showed that islets, but not exocrine tissue, were affected. The permeability increase seems to involve vasoactive substances released by mast cells. A mast cell inhibitor (disodium cromoglycate) and a serotonin antagonist (methysergide) were found protective. Furthermore, administration of methysergide partially prevented the development of hyperglycaemia in streptozotocin-treated rats. In mice, almost full protection from diabetes development was reached by both methysergide and disodium cromoglycate. Our observations indicate an important role of mast cell controlled membrane permeability in this model of beta-cell destruction and diabetes development.
Animals↗
L3T4 and Lyt-2 T cells are both involved in the generation of low-dose streptozotocin-induced diabetes in mice.
In order to determine the role of different T lymphocyte subsets in the pathogenesis of low-dose streptozotocin (LD-Sz) induced diabetes, we treated mice with Sz together with repeated injections of rat monoclonal antibodies (MoAb) with specificity towards the mouse T cell differentiation markers L3T4 ('helper/inducer' T cells and some macrophages), Lyt-2 ('cytotoxic/suppressor' T cells and NK cells) and Thy-1 (pan T lymphocytes). Treatment depleted target cells in peripheral blood and spleen; decreased the ability of spleen cells to respond to mitogens; and, in the case of depletion of the L3T4 T cell subset, prevented a humoral immune response to SRBC. Treatment with MoAb against either of the two T cell subtypes could protect from hyperglycaemia and loss of body weight, suggesting that both T cell subsets were implicated in the development of LD-Sz induced diabetes. Immunocytochemical analysis of pancreatic sections showed that both L3T4+ and Lyt-2+ cells participated in islet infiltration together with macrophages. Treatment with MoAb markedly reduced islet infiltration by both L3T4+ and Lyt-2+ cells but not by macrophages. The suppressive effect of MoAb against either L3T4 or Lyt-2 on diabetes development suggests that the pathomechanism involved is different from that in experimental autoimmune neuritis and adjuvant arthritis where Lyt-2 cells are not involved.
Animals↗
Analysis of 22 immunomodulatory substances for efficacy in low-dose streptozotocin-induced diabetes.
Of 22 immunomodulatory substances screened 12 were effective in modulating the course of hyperglycemia following low dose streptozotocin treatment. In this animal model diabetes is induced by administration of low doses of streptozotocin (30-40 mg/kg) body weight to male C57BL/6J/Bom, C57BL/KsJ and C3H/He/Bom mice on 5 consecutive days. Conventional immunosuppressants (azathioprine, cyclophosphamide) largely protected from diabetes development. Partial suppression of hyperglycemia was also seen after administration of B. pertussis, fetal tissue extracts, FTS, inosine pranobex, metronidazole and ADA 202-718. The majority of these substances, when applied with another regimen, and TP5 caused enhancement of diabetes. In conclusion, several substances with a therapeutic potential in experimental diabetes have been identified. Those with little risk of side-effects may deserve further analysis.
Adjuvants, Immunologic↗
[Cyclosporin A as a diabetogenic cofactor].
Two kidney transplanted patients are reported, who developed an insulin dependent diabetes mellitus after crossing therapeutic Cyclosporine A levels. After stabilisation of the Cyclosporine A levels the insulin dependent diabetes mellitus was completely reversible. The results are indicating Cyclosporine A as the insulin dependent diabetes mellitus initiator.
Adult↗
Immunosuppressive drugs in diabetes.
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Azathioprine↗
Cone synapses with Golgi-stained bipolar cells that are morphologically similar to a center-hyperpolarizing and a center-depolarizing bipolar cell type in the turtle retina.
Two types of Golgi-stained bipolar cells have been examined by light and electron microscopy to determine the ultrastructure of their synapses with photoreceptors and the spectral type of photoreceptor with which they connect in the retina of the turtle (Pseudemys scripta elegans). We have chosen bipolar cells that correspond in morphology to a center-hyperpolarizing type (H-bipolar) and a center-depolarizing type (D-bipolar) shown in Marchiafava and Weiler's paper (Proc. R. Soc. B 208:103-113, '80). The latter authors recorded intracellular responses and marked their cells with the fluorescent dye Procion yellow so that we have a clear picture of their morphology. These bipolars have been called B4 and B6, respectively, according to our recent classification scheme of Golgi-stained cells. Serial section electron microscopy of two B4 bipolars shows that they made wide-cleft, striated basal junctions with red and green cone pedicles. They connected to six or seven different cone pedicles. The three B6 bipolar cells studied made narrow-cleft, semi-invaginating basal junctions with cone pedicles. The dendrites of B6 bipolars did not become central elements at ribbon synapses although they invaginated toward the synaptic ribbon. Serial section electron microscopy indicated that B6 bipolars contacted three to five cone pedicles also of a red or green cone type. We suggest that in the case of these two varieties of bipolar cell in turtle retina, sign-conserving synapses with cones are wide-cleft basal junctions while sign-inverting synapses are narrow-cleft, semi-invaginating in morphology.
Animals↗
Recombinant interleukin 2 enhances spontaneous insulin-dependent diabetes in BB rats.
Treatment of BB rats with recombinant interleukin 2 (IL2) enhanced the development of spontaneous diabetes in these animals. A dose of 20 micrograms IL 2/kg body weight was administered twice daily for 80 days starting at 42 days of age. The rate of diabetes was doubled after IL 2 administration (53% vs. 23%) and the onset of diabetes was found to be accelerated by a mean of 18 days. Histological analysis showed enhanced inflammation of islets and in addition interstitial pancreatis. It is concluded that IL 2 has a regulatory effect on spontaneous organ-specific autoimmunity.
Animals↗
Endocytosis via galactose receptors in vivo. Ligand size directs uptake by hepatocytes and/or liver macrophages.
We followed the intrahepatic binding and uptake of variously sized ligands with terminal galactosyl residues in rat livers. The ligands were administered to prefixed livers in binding studies and in vivo and in situ (serum-free perfused livers) in uptake studies. Gold sols with different particle diameters were prepared: 5 nm (Au5), 17 nm (Au17), 50 nm (Au50) and coated with galactose exposing glycoproteins (asialofetuin (ASF) or lactosylated BSA (LacBSA)). Electron microscopy of mildly prefixed livers perfused with LacBSA-Au5 in serum-free medium showed ligand binding to liver macrophages, hepatocytes and endothelial cells. Ligands bound to prefixed cell surfaces reflect the initial distribution of receptor activity: pre-aggregated clusters of ligands are found on liver macrophages, single particles statistically distributed on hepatocytes and pre-aggregated clusters of particles restricted to coated pits on endothelial cells. Ligand binding is prevented in the presence of 80 mM N-acetylgalactosamine (GalNAc), while N-acetylglucosamine (GlcNAc) is without effect. Electron microscopy of livers after ligand injection into the tail vein shows that in vivo uptake of electron-dense galactose particles by liver cells is size-dependent. Using a LacBSA-Au preparation with heterogeneous particle diameter (2.2-11.7 nm) we found that hepatocytes take up only ligands up to the size of 7.8 nm, whereas particles of all sizes available in this experiment are found in liver macrophages and endothelial cells. ASF-Au17 and LacBSA-Au17 are endocytosed by liver macrophages and endothelial cells, but not by hepatocytes. ASF-Au50 is taken up by liver macrophages only. In vivo uptake by liver macrophages is mediated by galactose-specific recognition as shown by inhibition with GalNAc. Some 52-65% inhibition was measured in in vivo experiments and 78% inhibition in in situ experiments. GlNAc showed no inhibitory effect. Furthermore, we measured uptake of [125J]ASF and of [125J]ASF adsorbed to Au17 by the different cell populations of rat livers in vivo. While the bulk of the molecular ligand is found in the hepatocyte fraction, the particulate ligand is located in the sinusoidal fraction.
Animals↗
Inhibition of immune-mediated low-dose streptozotocin diabetes by agents which reduce vascular permeability.
Low-dose streptozotocin treatment in C57Bl/6J mice causes development of hyperglycemia within two weeks. Diabetes development is due to the specific loss of beta cells from pancreatic islets which can be blocked by immunosuppressive treatment. The role of vascular permeability in pancreatic islet destruction was studied by administration of methysergide or pargyline in addition to low-dose streptozotocin. Both drugs impair serotonin-enhanced vascular permeability. Administration of methysergide or pargyline during the first 11 days following streptozotocin treatment caused substantial suppression of diabetes development. These observations suggest a role of enhanced vascular permeability in immune-mediated beta cell destruction.
Animals↗
Administration of silica or monoclonal antibody to Thy-1 prevents low-dose streptozotocin-induced diabetes in mice.
Multiple injections of low doses of streptozotocin induce an experimental diabetes in mice. We have analyzed in two inbred strains whether the development of hyperglycaemia can be influenced by administration of macrophage-toxic silica particles or by a monoclonal antibody to Thy-1.2. Mice received streptozotocin (30 or 40 mg/kg) on five consecutive days (day 0-day 4) and in addition either silica particles (starting at day 0) or anti-Thy-1.2 (starting at day -2 or -3). In both strains mice receiving streptozotocin alone became hyperglycaemic within two weeks. Additional treatment with silica almost fully prevented diabetes development. Anti-Thy-1.2 administration was similarly effective in C57B1/Ks and partially protective in C57BL/6 mice. Histological analysis of pancreatic islets showed that a large fraction of beta cells had been spared from destruction by this treatment. The data indicate a role for both macrophages and Thy-1 positive cells in the pathogenesis of low-dose streptozotocin-induced diabetes.
Animals↗
Suppression of spontaneous insulin-dependent diabetes in BB rats by administration of ciamexone.
BB rats spontaneously develop an insulin dependent diabetes which resembles in many features human type I diabetes. We have tested the effect of the immunomodulatory drug Ciamexone, a 2-cyan-aziridine-derivative, on the development of diabetes in BB rats. Ciamexone was given once daily during 6 days per week beginning with the age of 42 or 50 days up to 120 days. For comparison cyclosporin A (10 mg/kg) was applied following the same protocol. At 1 mg/kg ciamexone administration led to complete prevention of diabetes in females but was not beneficial in males. At 10 mg/kg the drug caused significant suppression of diabetes development in males but more pronounced in females. Both, a reduction of the incidence of diabetes and a delay in the onset of hyperglycaemia was observed only in females. After administration of cyclosporin A none of the animals developed diabetes. Ciamexone treatment did not affect granulocyte and lymphocyte counts and subsets in the peripheral blood except for a tendency to suppress eosinophilia. The growth of animals was not retarded. It is concluded that ciamexone seems to influence the autoimmune state of the BB rat resulting in partial suppression of the disease.
Aging↗
Large increase of cytotoxic/suppressor T-lymphoblasts and eosinophils around manifestation of diabetes in BB rats.
In order to gain more insight into the pathogenetic mechanism leading to beta cell destruction in BB rats we searched for specific changes in the immune system at the time of diabetes development. We performed a density gradient fractionation of all major leukocyte types in the peripheral blood and the spleen of acutely diabetic or non-diabetic BB rats as well as of normal Wistar rats in order to identify proliferating low density blasts. Acutely diabetic BB rats showed a 4-6 times higher percentage of lymphoblasts among spleen cells than non-diabetic BB or Wistar rats. The majority of blasts was of the T-cytotoxic/suppressor (Ox8+) phenotype (61%) in acutely diabetic BB rats, but of the T-helper (W3/25+) phenotype (51%) in non-diabetic BB or Wistar rats. Plasma cell and monocyte numbers were not increased in acutely diabetic BB rats. At the time of diabetes manifestation BB rats develop a pronounced eosinophilia. These observations indicate a state of enhanced cellular immunity involving cytotoxic/suppressor T cells during diabetes development in BB rats.
Animals↗