Biomedical subjects

D Stern

Publications and source records attributed to D Stern.

At least 19 recordsLinked to original sources

PubMed1996

Receptor-mediated endothelial cell dysfunction in diabetic vasculopathy. Soluble receptor for advanced glycation end products blocks hyperpermeability in diabetic rats.

Dysfunctional endothelium is associated with and, likely, predates clinical complications of diabetes mellitus, by promoting increased vascular permeability and thrombogenicity. Irreversible advanced glycation end products (AGEs), resulting from nonenzymatic glycation and oxidation of proteins or lipids, are found in plasma, vessel wall, and tissues and have been linked to the development of diabetic complications. The principal means through which AGEs exert their cellular effects is via specific cellular receptors, one of which, receptor for AGE (RAGE), is expressed by endothelium. We report that blockade of RAGE inhibits AGE-induced impairment of endothelial barrier function, and reverse, in large part, the early vascular hyperpermeability observed in diabetic rats. Inhibition of AGE- and diabetes-mediated hyperpermeability by antioxidants, both in vitro and in vivo, suggested the central role of AGE-RAGE-induced oxidant stress in the development of hyperpermeability. Taken together, these data support the concept that ligation of AGEs by endothelial RAGE induces cellular dysfunction, at least in part by an oxidant-sensitive mechanism, contributing to vascular hyperpermeability in diabetes, and that RAGE is central to this pathologic process.

Adult↗

PubMed1995

Functional interactions of T cells with endothelial cells: the role of CD40L-CD40-mediated signals.

CD40 is expressed on a variety of cells, including B cells, monocytes, dendritic cells, and fibroblasts. CD40 interacts with CD40L, a 30-33-kD activation-induced CD4+ T cell surface molecule. CD40L-CD40 interactions are known to play key roles in B cell activation and differentiation in vitro and in vivo. We now report that normal human endothelial cells also express CD40 in situ, and CD40L-CD40 interactions induce endothelial cell activation in vitro. Frozen sections from normal spleen, thyroid, skin, muscle, kidney, lung, or umbilical cord were studied for CD40 expression by immunohistochemistry. Endothelial cells from all tissues studied express CD40 in situ. Moreover, human umbilical vein endothelial cells (HUVEC) express CD40 in vitro, and recombinant interferon gamma induces HUVEC CD40 upregulation. CD40 expression on HUVEC is functionally significant because CD40L+ Jurkat T cells or CD40L+ 293 kidney cell transfectants, but not control cells, upregulate HUVEC CD54 (intercellular adhesion molecule-1), CD62E (E-selectin), and CD106 (vascular cell adhesion molecule-1) expression in vitro. Moreover, the kinetics of CD40L-, interleukin 1-, or tumor necrosis factor alpha-induced CD54, CD62E, and CD106 upregulation on HUVEC are similar. Finally, CD40L-CD40 interactions do not induce CD80, CD86, or major histocompatibility complex class II expression on HUVEC in vitro. These results demonstrate that CD40L-CD40 interactions induce endothelial cell activation in vitro. Moreover, they suggest a mechanism by which activated CD4+ T cells may augment inflammatory responses in vivo by upregulating the expression of endothelial cell surface adhesion molecules.

Antigens, CD↗

PubMed1995

Cloning of a novel RNA binding polypeptide (RA301) induced by hypoxia/reoxygenation.

Astrocytes have a critical role in the neuronal response to ischemia, as their production of neurotrophic mediators can favorably impact on the extreme sensitivity of nervous tissue to oxygen deprivation. Using a differential display method, a novel putative RNA binding protein, RA301, was cloned from reoxygenated astrocytes. Analysis of the deduced amino acid sequence showed two ribonucleoprotein domains and serine/arginine-rich domains, suggestive of their function as RNA splicing factor. Northern analysis displayed striking induction only in cultured astrocytes within 15 min of reoxygenation and reached a maximum by 60 min after hypoxia/reoxygenation. Immunoblotting demonstrated expression of an immunoreactive polypeptide of the expected molecular mass, 36 kDa, in lysates of hypoxia/reoxygenated astrocytes. Induction of RA301 mRNA was mediated, in large part, by endogenously generated reactive oxygen species, as shown by diphenyl iodonium, an inhibitor of neutrophil-type nicotinamide adenine dinucleotide phosphate oxidase which blocks oxygen-free radical formation by astrocytes. Similarly, increased expression of RA301 in supporting a neurotrophic function of astrocytes was suggested by inhibition of interleukin-6 elaboration, a neuroprotective cytokine, in the presence of antisense oligonucleotide for RA301. These studies provide a first step in characterizing a novel putative RNA binding protein, whose expression is induced by oxygen-free radicals generated during hypoxia/reoxygenation, and which may have an important role in redirection of biosynthetic events observed in the ischemic tissues.

Aerobiosis↗

PubMed1995

Induction of interleukin 6 (IL-6) by hypoxia in vascular cells. Central role of the binding site for nuclear factor-IL-6.

The pathologic picture in ischemic tissue injury shares features with the inflammatory response, including production of proinflammatory cytokines. Hypoxia-mediated induction of interleukin-6 (IL-6), a cytokine with anti-inflammatory properties, could set in motion mechanisms limiting inflammation in ischemia. Exposure of cultured endothelial cells (ECs) to H (pO2 approximately 12-16 torr) increased transcription of IL-6, elevated levels of IL-6 mRNA, and induced elaboration of IL-6 antigen in a time-dependent manner. Exposure of mice to hypoxia increased IL-6 transcripts in the lung, and immunostaining revealed a striking increase in IL-6 antigen in pulmonary vasculature. Transfection of ECs with deletion chimeric IL-6 promoter-chloramphenicol acetyl-transferase (CAT) constructs showed hypoxia-mediated 9-11-fold induction with -1200/+13, -596/+13, and -225/+13 but no induction with -111/+13. Electrophoretic mobility shift assays (EMSAs) using -225/-111 as the labeled probe demonstrated enhanced binding activity in nuclear extracts of hypoxic ECs and lung; the appearance of the gel shift band was prevented by excess unlabeled probe (-225/-111), and hypoxia-mediated enhancement of the band was blocked by a probe corresponding to the nuclear factor (NF)-IL-6 site (-158/-145). The hypoxia-enhanced band on EMSA displayed a supershift with antibody to CCAAT-enhancer-binding protein beta (C/EBP-beta), but antibody to C/EBP-alpha or -delta was without effect. Transfection of ECs with a construct comprising thymidine kinase promoter, -225/-111 in either the 5' to 3' to 5' orientation, and the reporter CAT showed this region to be an enhancer (approximately 8-fold) under hypoxia. EMSA with the NF-IL-6 probe revealed a prominent induction of binding activity with nuclear extracts from hypoxic ECs and whole lung. Constructs with -158/-145 and the CAT reporter gene showed induction when transfected into hypoxic ECs, whereas a similar construct with the NF-IL-6 motif mutationally inactivated failed to display hypoxia-induced expression. Furthermore, the tumor necrosis factor (TNF) gene, whose product contributes to ischemic pathology and contains a putative regulatory NF-IL-6 site, demonstrated enhanced binding activity for its NF-IL-6 motif and induction of TNF mRNA based on analysis of hypoxic lung. These data indicate that hypoxia induces expression of IL-6, most likely a result of hypoxic activation at the NF-IL-6 site, and suggest that other genes with regulatory NF-IL-6 sites may also be induced by a similar mechanism.

Animals↗

PubMed1995

Synthesis, antioxidant properties, biological activity and molecular modelling of a series of chalcogen analogues of the 5-lipoxygenase inhibitor DuP 654.

2-Phenylsulfenyl- (1b), 2-phenylselenenyl- (1c) and 2-phenyltellurenyl-1-naphthol (1d) were prepared and their antioxidative properties evaluated in comparison with 2-benzyl-1-naphthol (1a; DuP 654). 2-Phenyltellurenyl-1-naphthol had a significantly lower (1.00 V versus SCE) oxidation potential than the other three compounds (1.24, 1.27 and 1.25 V, respectively, versus SCE for compounds 1a, 1b and 1c) as determined by cyclic voltammetry. In contrast to the other materials, compound 1d was able to catalyze the reduction of hydrogen peroxide in the presence of thiols as stoichiometric reducing agents. The organotellurium compound was also the most efficient inhibitor of azo-initiated peroxidation of linoleic acid in a two-phase model system. Ab initio geometry optimization at the 3-21G(*) level revealed infinitesimal changes in the molecular conformations of the carbon, sulfur, selenium and tellurium analogues. As judged by their ability to inhibit stimulated LTB4 biosynthesis in human neutrophils, compounds 1a-1d all turned out to be highly potent 5-lipoxygenase inhibitors with IC50-values ranging from 0.40 microM for 2-benzyl-1-naphthol (1a) to 0.063 microM for 2-phenyltellurenyl-1-naphthol (1d).

Antioxidants↗

PubMed1995

Asymmetric processing of coding ends and the effect of coding end nucleotide composition on V(D)J recombination.

The products of V(D)J recombination are coding and signal joints. We show that the nucleotide composition of the coding ends affects V(D)J recombination. The presence of Ts at the 5' end of either the 12 mer or the 23 mer recombination signal sequence (RSS) greatly decreases coding and signal joint formation, and Ts at the 5' ends of both RSSs eliminate recombination, suggesting that a step during the initiation phase of the recombination is affected. A 5' T coding end can be rescued it the other end contains 5' G, C, or A, implying that synapsis may be required. Furthermore, the presence of As at the 5' end of the 12 mer, but not the 23 mer, RSS affects coding but not signal joint formation. This observation of asymmetric processing of coding ends suggests that different protein complexes are bound to the two RSSs, and become transferred to the aligned coding ends during processing.

B-Lymphocytes↗

PubMed1995

Advanced glycation endproducts interacting with their endothelial receptor induce expression of vascular cell adhesion molecule-1 (VCAM-1) in cultured human endothelial cells and in mice. A potential mechanism for the accelerated vasculopathy of diabetes.

Vascular cell adhesion molecule-1 (VCAM-1), an inducible cell-cell recognition protein on the endothelial cell surface (EC), has been associated with early stages of atherosclerosis. In view of the accelerated vascular disease observed in patients with diabetes, and the enhanced expression of VCAM-1 in diabetic rabbits, we examined whether irreversible advanced glycation endproducts (AGEs), could mediate VCAM-1 expression by interacting with their endothelial cell receptor (receptor for AGE, RAGE). Exposure of cultured human ECs to AGEs induced expression of VCAM-1, increased adhesivity of the monolayer for Molt-4 cells, and was associated with increased levels of VCAM-1 transcripts. The inhibitory effect of anti-RAGE IgG, a truncated form of the receptor (soluble RAGE) or N-acetylcysteine on VCAM-1 expression indicated that AGE-RAGE-induced oxidant stress was central to VCAM-1 induction. Electrophoretic mobility shift assays on nuclear extracts from AGE-treated ECs showed induction of specific DNA binding activity for NF-kB in the VCAM-1 promoter, which was blocked by anti-RAGE IgG or N-acetylcysteine. Soluble VCAM-1 antigen was elevated in human diabetic plasma. These data are consistent with the hypothesis that AGE-RAGE interaction induces expression of VCAM-1 which can prime diabetic vasculature for enhanced interaction with circulating monocytes.

Animals↗

PubMed1995

Interaction of antibody with Forssman antigen in guinea pigs. A mechanism of adaptation to antibody- and complement-mediated injury.

Forssman antigen is a glycosphingolipid with antigenic specificity determined by extra-membrane haptenic sugars similar to blood group antigens and antigens that are the main barrier to xenogeneic organ transplantation. Herein, we describe the localization of Forssman antigen in guinea pig lungs and kidneys and the consequences of its interaction with antibodies in vitro and in vivo (Forssman reaction). Exposure of cultured guinea pig aortic endothelial cells to Forssman antibodies induced rapid redistribution of antigen-antibody complexes at the cell surface, followed by shedding that occurred by blebbing of plasma membrane as vesicles or fragments, and was associated with disappearance of antigen from the cell surface (antigenic modulation). Guinea pigs surviving frequent intravenous infections of increasing amounts of antibodies, for a total of 20 to 40 lethal doses, developed a partial or complete adaptation to generalized Forssman reaction, and adaptation was associated with partial or complete modulation of Forssman antigen at the surface of the pulmonary and, in minor degree, renal endothelial and epithelial cells. These findings support the hypothesis that modulation of endothelial carbohydrate antigens contributes to adaptation of highly vascularized organs exposed to tolerable levels of allo- or xenoantibodies.

Animals↗

PubMed1994

Advanced Maillard reaction end products are associated with Alzheimer disease pathology.

During aging long-lived proteins accumulate specific post-translational modifications. One family of modifications, termed Maillard reaction products, are initiated by the condensation between amino groups of proteins and reducing sugars. Protein modification by the Maillard reaction is associated with crosslink formation, decreased protein solubility, and increased protease resistance. Here, we present evidence that the characteristic pathological structures associated with Alzheimer disease contain modifications typical of advanced Maillard reaction end products. Specifically, antibodies against two Maillard end products, pyrraline and pentosidine, immunocytochemically label neurofibrillary tangles and senile plaques in brain tissue from patients with Alzheimer disease. In contrast, little or no staining is observed in apparently healthy neurons of the same brain. The Maillard-reaction-related modifications described herein could account for the biochemical and insolubility properties of the lesions of Alzheimer disease through the formation of protein crosslinks.

Alzheimer Disease↗

PubMed1994

The endothelial cell binding site for advanced glycation end products consists of a complex: an integral membrane protein and a lactoferrin-like polypeptide.

Advanced glycation end products (AGEs), formed as the result of the extended interaction of proteins with ketoses, modulate central properties of endothelial cells and mononuclear phagocytes by interacting with a cell surface binding site comprised of a novel integral membrane protein (receptor for AGE = RAGE) and a lactoferrin-like polypeptide (LF-L), the latter having sequence identity to lactoferrin (LF). To further understand this cellular binding site, the interaction of RAGE with LF-L and LF was characterized. By ligand blotting and a solid state competitive binding assay, 125I-LF-L and 125I-LF bound to RAGE immobilized on nitrocellulose membranes or polypropylene tubes in a time-dependent and reversible manner, demonstrating a high affinity component with Kd approximately 100 pM. The interaction of 125I-LF-L and 125I-LF with RAGE was independent of iron in LF and was competed by addition of an excess of unlabeled carboxyl-terminal portion of LF. Cross-linking studies with purified 125I-LF-L and RAGE, in the presence of disuccinimidyl suberate, showed a new, slowly migrating band, corresponding to a complex of RAGE and LF-L, and cross-linking on mouse aortic endothelial cells showed two new slowly migrating bands on immunoblotting visualized with both anti-RAGE IgG and anti-LF-L IgG. These data lead us to propose that the endothelial cell surface binding site for AGEs consists of LF-L bound noncovalently to RAGE anchored in the cell membrane.

Amino Acid Sequence↗

PubMed1994

Enhanced cellular oxidant stress by the interaction of advanced glycation end products with their receptors/binding proteins.

Attack by reactive oxygen intermediates, common to many kinds of cell/tissue injury, has been implicated in the development of diabetic and other vascular diseases. Such oxygen-free radicals can be generated by advanced glycation end products (AGEs), which are nonenzymatically glycated and oxidized proteins. Since cellular interactions of AGEs are mediated by specific cellular binding proteins, receptor for AGE (RAGE) and the lactoferrin-like polypeptide (LF-L), we tested the hypothesis that AGE ligands tethered to the complex of RAGE and LF-L could induce oxidant stress. AGE albumin or AGEs immunoisolated from diabetic plasma resulted in induction of endothelial cell (EC) oxidant stress, including the generation of thiobarbituric acid reactive substances (TBARS) and resulted in the activation of NF-kappa B, each of which was blocked by antibodies to AGE receptor polypeptides and by antioxidants. Infusion of AGE albumin into normal animals led to the appearance of malondialdehyde determinants in the vessel wall and increased TBARS in the tissues, activation of NF-kappa B, and induction of heme oxygenase mRNA. AGE-induced oxidant stress was inhibited by pretreatment of animals with either antibodies to the AGE receptor/binding proteins or antioxidants. These data indicate that interaction of AGEs with cellular targets, such as ECs, leads to oxidant stress resulting in changes in gene expression and other cellular properties, potentially contributing to the development of vascular lesions. Further studies will be required to dissect whether oxidant stress occurs on the cell surface or at an intracellular locus.

Adrenal Glands↗

PubMed1994

Therapeutic alliance on an inpatient unit for eating disorders.

The therapeutic alliance as measured by the Working Alliance Inventory was examined on an inpatient unit for eating disorders. Unit staff and patients (n = 33) admitted within a 2-year period completed the rating scales at 3 weeks after admission and again at 8 weeks. Patients who remained in the program (n = 21) perceived the therapeutic alliance with staff to be significantly stronger than patients who left the program (n = 10). The perception of the alliance strengthened over time for patients while staff perceptions did not. Little correlation was observed between staff and patient perceptions of the alliance. The findings suggest that patient perception of the alliance may be a critical factor in the decision to remain in the treatment program. It is argued that helping a patient feel involved in a structured program presents a particular challenge to staff.

Adult↗

PubMed1994

Phthalocyanine photodynamic therapy: new strategy for closure of choroidal neovascularization.

Chloro-aluminum sulfonated phthalocyanine (CASPc) is a photo-chemically active dye employed in photodynamic therapy (PDT). CASPc is a potent generator of singlet oxygen when irradiated with 675 nm light and is also capable of fluorescence, allowing visualization of the dye in tissues. We devised an angiography system using CASPc fluorescence to determine its localization in experimental choroidal neovascularization in monkeys and then investigated the ability of CASPc to produce photochemical closure of neovascularization upon irradiation with 675nm laser light. Fluorescent imaging indicated that CASPc localized angiographically in areas of neovascularization for at least 24 hours. Irradiation with 675 nm laser light 5-30 minutes after CASPc injection produced complete closure of choroidal neovascularization with minimal damage to overlying retina. We conclude that CASPc localizes in neovascular choroidal vessels and that CASPc photodynamic therapy can produce closure of these choroidal vessels.

Aluminum↗

PubMed1994

FPTT is a low-incidence Rh antigen associated with a "new" partial Rh D phenotype, DFR.

BACKGROUND: Several Rh D phenotypes with partial D antigens are recognized. Some partial D antigens are associated with low-incidence Rh antigens. New partial D antigens are revealed by an atypical pattern of reactions with anti-D. STUDY DESIGN AND METHODS: The reactions of D variant cells with panels of monoclonal anti-D and with antibodies to low-incidence antigens were compared to those of known D categories to identify a new Rh D phenotype. The inheritance of partial D antigens was studied by Rh phenotyping of the families of the probands. Standard serologic methods were used and family data were analyzed. RESULTS: A new Rh D phenotype, to be called DFR, was identified in 17 probands, two of whom had made anti-D. The partial D antigen carries epD3, epD4, and epD9 and lacks epD8. The presence of other D epitopes is ambiguous; different answers were obtained for the same sample with different monoclonal anti-D of the same apparent epitope specificity. The immunoglobulin class of the anti-D was important: IgG were more successful than IgM monoclonal anti-D in detecting the partial D of DFR. Family studies showed that DFR traveled with Ce more frequently than with cE. The low-incidence antigen FPTT (International Society of Blood Transfusion number 700048) was found on all DFR samples. Family studies demonstrated that FPTT is, as suspected, part of the complex Rh system. CONCLUSION: The partial D of the Rh D phenotype, DFR, is recognized by its pattern of reactions with monoclonal anti-D and its association with the low-incidence antigen FPTT, FPTT has now been numbered Rh50.

Antibodies, Monoclonal↗

PubMed1994

Cellular receptors for advanced glycation end products. Implications for induction of oxidant stress and cellular dysfunction in the pathogenesis of vascular lesions.

Advanced glycation end products (AGEs) form by the interaction of aldoses with proteins and the subsequent molecular rearrangements of the covalently linked sugars, eventuating in a diverse group of fluorescent compounds of yellow-brown color. This heterogeneous class of nonenzymatically glycated proteins or lipids is found in the plasma and accumulates in the vessel wall and tissues even in normal aging. As a consequence of hyperglycemia, AGE formation and deposition are much enhanced in diabetes, in which their presence has been linked to secondary complications, especially microvascular disease. This review summarizes the cellular interactions of AGEs and describes the central role of a novel receptor for AGE (RAGE). RAGE, an immunoglobulin superfamily member, mediates the binding of AGEs to endothelial cells and mononuclear phagocytes, interacts with a lactoferrin-like polypeptide that also binds AGEs, and appears to activate intracellular signal transduction mechanisms consequent to its interaction with the glycated ligand. RAGE is expressed by ECs, mononuclear phagocytes, smooth muscle cells, mesangial cells, and neurons, indicating a potential role in the regulation of their properties in homeostasis and/or their dysfunction in the development of diabetic complications. Since AGEs have been shown to generate reactive oxygen intermediates, tethering of AGEs to the cell surface by their receptors focuses oxidant stress on cellular targets, resulting in changes in gene expression and the cellular phenotype. The discovery of RAGE and development of reagents to block its interaction with AGEs should provide insights into the role of this ligand-receptor interaction in the pathogenesis of diabetic complications and, potentially, atherosclerosis.

Animals↗

PubMed1994

Hypoxic induction of interleukin-8 gene expression in human endothelial cells.

Because leukocyte-mediated tissue damage is an important component of the pathologic picture in ischemia/reperfusion, we have sought mechanisms by which PMNs are directed into hypoxic tissue. Incubation of human endothelial cells (ECs) in hypoxia, PO2 approximately 14-18 Torr, led to time-dependent release of IL-8 antigen into the conditioned medium; this was accompanied by increased chemotactic activity for PMNs, blocked by antibody to IL-8. Production of IL-8 by hypoxic ECs occurred concomitantly with both increased levels of IL-8 mRNA, based on polymerase chain reaction analysis, and increased IL-8 transcription, based on nuclear run-on assays. Northern analysis of mRNA from hypoxic ECs also demonstrated increased levels of mRNA for macrophage chemotactic protein-1, another member of the chemokine superfamily of proinflammatory cytokines. IL-8 gene induction was associated with the presence of increased binding activity in nuclear extracts from hypoxic ECs for the NF-kB site. Studies with human umbilical vein segments exposed to hypoxia also demonstrated increased elaboration of IL-8 antigen compared with normoxic controls. In mice exposed to hypoxia (PO2 approximately 30-40 Torr), there was increased pulmonary leukostasis, as evidenced by increased myeloperoxidase activity in tissue homogenates. In parallel, increased levels of transcripts for IP-10, a murine homologue in the chemokine family related to IL-8, were observed in hypoxic lung tissue. Taken together, these data suggest that hypoxia constitutes a stimulus for leukocyte chemotaxis and tissue leukostasis.

Animals↗

PubMed1994

Heme oxygenase-1 is associated with the neurofibrillary pathology of Alzheimer's disease.

Heme oxygenase-1 is an important enzyme that degrades heme, a pro-oxidant, leading to the formation of antioxidant molecules. In this study we demonstrate by immunocytochemistry close association of heme oxygenase-1 with Alzheimer neurofibrillary pathology and with the neurofibrillary tangles found in progressive supranuclear palsy and subacute sclerosing panencephalitis. In Alzheimer's disease, using two different rabbit antisera against heme oxygenase-1 protein, we localized, using immunocytochemical methods, heme oxygenase-1 to neurofibrillary tangles, senile plaque neurites, granulovacuolar degeneration, and neuropil threads. Only light background staining was seen in young controls and sporadic lesion-related immunoreactivity in age-matched controls. The increase in heme oxygenase-1 protein in association with the neurofibrillary pathology of Alzheimer's disease and other diseases characterized by neurofibrillary tangles supports the notion that the generation of free radicals and oxidative stress plays a role in the pathogenesis of neurofibrillary pathology.

Aged↗

PubMed1993

Antibody-mediated redistribution and shedding of endothelial antigens in the rabbit.

We report the results of studies performed in vitro and in vivo that were designed to explore individual, sequential, and concurrent Ag-antibody interactions at the surface of rabbit endothelial cells. Divalent heterologous antibodies to rabbit lung angiotensin-converting enzyme and to rabbit lung thrombomodulin were employed. In cultured monolayers, both antibodies redistributed the specific Ag and co-redistributed the immunologically unrelated Ag inducing partial or complete disappearance of the Ag from the cell surface (antigenic modulation) in 15 to 60 min. When injected into living rabbits, each antibody induced a rapid (1 to 3 min) redistribution and subsequent modulation of the specific and of the unrelated Ag at the surface of alveolar endothelial cells. Immune complexes, and the unrelated Ag, were shed in the circulation, attaining peak levels 3 to 4 min after the injection; were rapidly bound by platelets, E, and polymorphonuclear leukocytes; and were subsequently found in phagocytic cells in the spleen and in the liver. Thrombomodulin co-shed by angiotensin-converting enzyme antibody and, to a lesser degree, angiotensin-converting enzyme co-shed by thrombomodulin antibody, crossed the glomerular capillary walls and were reabsorbed by the epithelial cells of the proximal tubules within 2 to 3 min. The results show that immunologically unrelated Ag can be passively entrapped during formation of immune complexes at the cell surface, and provide new information on the kinetics of clearance of immune complexes containing endogenous, structural Ag.

Animals↗