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Biomedical subjects

T Caulin-Glaser

Publications and source records attributed to T Caulin-Glaser.

8 recordsLinked to original sources
PubMed1996

Effects of 17beta-estradiol on cytokine-induced endothelial cell adhesion molecule expression.

One of the earliest events in atherosclerosis is interaction of circulating mononuclear leukocytes and the endothelium. Endothelial cell (EC) activation by cytokines results in expression of adhesion molecules and production of chemotactic factors, augmenting leukocyte adhesion and recruitment, respectively. The incidence of atherosclerosis in premenopausal women is significantly less than that observed in age-matched males with similar risk profiles. Because estrogen has gene regulatory effects, we investigated whether 17beta-estradiol (E2) can inhibit cytokine-mediated EC adhesion molecule transcriptional activation. Cultured human umbilical vein EC (estrogen receptor-positive) were propagated in gonadal hormone-free medium and were E2-pretreated for 48 h before IL-1 activation. Detected by FACS analysis, E2 strongly (60-80%) inhibited IL-1-mediated membrane E-selectin and vascular cell adhesion molecule-1 induction, and intercellular adhesion molecule-1 hyperinduction. 17alpha-estradiol (an inactive E2 stereoisomer) had no effect. This inhibition correlated with similar reductions in steady state-induced E-selectin mRNA levels, and was abrogated by the E2 antagonist ICI 164,384, demonstrating a specific, estrogen receptor-mediated effect. Nuclear run-offs confirmed suppression at the transcriptional level. The implications of these results for the cardiovascular protective role of estrogen are discussed.

Arteriosclerosis↗
PubMed1986

Interaction of immune complexes with glomerular heparan sulfate-proteoglycans.

The binding characteristics of cationic and more neutral immune complexes with heparan sulfate-proteoglycan enriched anionic sites of glomerular basement membrane and mesangial matrix were studied. Rat kidneys were treated either with buffers alone or buffers containing heparitinase or chondroitinase-ABC followed by perfusion with cationic or native immune complexes. Tissues were processed for immunofluorescence and transmission electron microscopy after fixation with glutaraldehyde or tannic acid glutaraldehyde. Kidneys perfused with radioiodinated immune complexes were processed for light and electron microscopic autoradiography. In addition, glomeruli from kidneys perfused with radioiodinated immune complexes were isolated and counted for radioactivity. By immunofluorescence the cationic immune complexes deposited linearly along the glomerular basement membrane. By electron microscopy, the cationic complexes localized mainly in the inner and outer layers of the glomerular basement membrane and to a certain extent in the mesangial matrix in a distribution that corresponded to previously documented anionic sites. Whereas heparitinase treatment abrogated the binding of cationic immune complexes in both glomerular basement membrane and mesangial matrix, chondroitinase-ABC treatment did not cause any decrease in binding. In contrast, more neutral immune complexes appeared to be nonspecifically trapped in the mesangium, and their distribution was unaffected by both enzymatic treatments. Light and electron microscopic autoradiography and counts of isolated glomeruli confirmed these findings. The results overall indicate that cationic immune complexes bind electrostatically to the heparan sulfate-proteoglycan enriched anionic sites of the glomerular basement membrane and mesangial matrix, while more neutral immune complexes are nonspecifically trapped in the mesangium of the renal glomerulus.

Animals↗
PubMed1985

Charge-related deposition of immune complexes in the glomerular basement membrane is independent of Fc effector function.

Differently charged immune complexes composed of fragments of bovine gamma globulin (BGG) antigen and fragments of rabbit anti-BGG antibody lacking FC portions were used for a study of the role of charge in deposition and localization within the mouse glomerulus. Preformed soluble complexes were made from native heterogeneous, cationic, or anionic F(ab')2 fragments of BGG and of rabbit antibody to BGG, and were injected intravenously. The distribution in the kidney was studied by immunofluorescence and electron microscopy. Cationic but not anionic or heterogeneous complexes diffusely localized in the glomerular basement membrane in both subepithelial and subendothelial sites. In contrast, more neutral or anionic complexes localized less prominently and were limited to the mesangium. The findings suggest that electrostatic interactions independent of Fc effector functions of immunoglobulins can be responsible for glomerular immune complex localization.

Animals↗
PubMed1983

Nondissociating cationic immune complexes can deposit in glomerular basement membrane.

The mechanisms by which immune complexes deposit in the glomerular basement membrane have been the subject of much debate, with the relative importance of direct deposition of circulating immune complexes (IC) vs. formation of IC in situ from the binding of circulating antibody to structural or exogenous planted antigen being at issue. In order to determine whether intact IC can deposit as such, covalently linked IC were prepared by a two-step reaction involving the bifunctional reagent toluene-2,4-diisocyanate (TDI), the antigen bovine gamma globulin (BGG), and rabbit anti-BGG antibody. Antigen and antibody were covalently cross-linked, with little self-linkage of antigen or antibody, and IC were purified by gel filtration. The net charge of the complexes was varied by chemical means, either before or after IC formation. When cationic IC were injected intravenously into mice, there was codeposition of antigen and antibody diffusely in the glomerular basement membrane (GBM), and deposits were observed ultrastructurally in the laminae rarae, interna and externa, and the lamina densa. Thus, under conditions of restricted appropriate charge, intact IC can cross the glomerular basement membrane and deposit in subepithelial sites without being excluded by size alone.

Animals↗
PubMed1983

Nephritogenicity and differential distribution of glomerular immune complexes related to immunogen charge.

Nephritogenicity and the differential distribution of glomerular deposits as a function of immunogen charge were examined in a murine model of chronic active serum sickness. A range of differentially charged immunogens was used, i.e., chemically modified highly cationic or anionic bovine gamma-globulin (BGG), native unmodified isoelectrically focused slightly cationic or anionic BGG, and heterogeneous native BGG. The amounts and distribution of immune complexes in glomeruli were compared by immunofluorescence and electron microscopy 3 to 10 weeks after the initiation of 15 intravenous injections of the five immunogens and 13 days after intraperitoneal continuous release of the native unmodified BGGs by osmotic pumps. The results demonstrate that the more cationic the immunogen, the more nephritogenic and the greater the tendency to form subepithelial deposits in the glomerular basement membrane. The observed differences in nephritogenicity and localization induced by focused unmodified cationic and anionic fractions of BGG particularly emphasize immunogen charge as a major factor influencing glomerular distribution of immune complexes in this model. The findings indicate that several degrees of nephritogenicity and the differential distribution of immune complexes can be related to immunogen charge and strongly suggest that charge interactions may be of fundamental importance in the pathogenesis of immune complex glomerulonephritis.

Animals↗
PubMed1982

Structural studies on an IgM-lambda pyroglobulin.

An IgM-lambda pyroglobulin from a patient with Waldenström's syndrome was studied. Heavy and light chains were separated and their N-terminal amino acid sequence determined. The heavy chain was unblocked and belonged to the VHIII subclass, and the light chain belonged to the lambda I subclass. Factors influencing pyroprecipitability were examined through experiments designed to study some of the physical and chemical properties of an IgM-lambda pyroglobulin. Pyroprecipitability was affected by pH, ionic strength, urea, and reducing agents, suggesting an involvement of noncovalent electrostatic interactions. It was also demonstrated through recombinant experiments that it is necessary to have covalently joined homologous heavy and light chains in pentameric form for pyroprecipitation to occur. Since neither heavy nor light chains had any unique structural features, the reasons for this property remain obscure but may reflect the result of conformational factors.

Amino Acid Sequence↗
PubMed1981

Charge of circulating immune complexes as a factor in glomerular basement membrane localization in mice.

The effect of the charge of circulating immune complexes on glomerular localization was studied in a model of passive serum sickness. Preformed immune complexes of heterogeneous or restricted charge, prepared in vitro from isoelectrically focused or chemically modified proteins, were injected intravenously into mice. The distribution of immune complexes in the kidney was compared by immunofluorescence and electron microscopy. Cationic but not anionic or electrophoretically heterogeneous immune complexes gave rise to diffuse localization in the glomerular basement membrane. The binding in subepithelial and subendothelial sites correlated with the known distribution of structural anionic sites. The observations suggest that electrostatic interactions between fixed anionic sites and immune complexes may be an important factor in glomerular trapping. Alternative mechanisms based on initial localization of excess free cationic antigen cannot be completely excluded and are also considered.

Animals↗