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C Esposito

Publications and source records attributed to C Esposito.

At least 127 records · Page 7Linked to original sources
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↗
PubMed1993

Mechanisms of cardiac pain during coronary angioplasty.

OBJECTIVES: This study was conducted to establish whether the cardiac pain patients experience during coronary angioplasty is modulated by 1) the stretching of the coronary artery wall, and 2) the mechanisms responsible for the ischemic preconditioning. BACKGROUND: Anecdotal experimental observations indicate that stretching of the coronary artery wall is a stimulus adequate to cause cardiac pain. Furthermore, recent experimental studies indicate that adenosine, a mediator of the anginal pain, appears to play an important role in the genesis of ischemic preconditioning. METHODS: We randomly allocated 48 consecutive patients undergoing coronary angioplasty into two groups. In Group A the second balloon inflation was performed at a higher level than the first; in Group B the first two inflations were performed at the same level of balloon pressure. The mean values (+/- 1 SD) of ST segment shift on the surface 12-lead electrocardiogram (ECG) and the intracoronary ECG were measured at the end of each inflation period. Severity of cardiac pain was also obtained at the same time by using a visual analog scale. RESULTS: The mean ST segment shift during the second balloon inflation was significantly less than that during the first inflation in both groups of patients (12.8 +/- 9.3 vs. 18.5 +/- 11.9 mm, p < 0.001 and 13.7 +/- 10.1 vs. 21.3 +/- 13.9 mm, p < 0.001, respectively, in Groups A and B). Yet, the severity of cardiac pain during the second inflation was greater than that during the first inflation in Group A (40.8 +/- 32.7 vs. 26.9 +/- 27.2 mm, p < 0.01), whereas it was lesser in Group B (23.1 +/- 20.7 vs. 32.9 +/- 29.6 mm, p < 0.05). However, in the latter group, pain severity after normalization for the mean ST segment shift was similar during the first and second inflations (2.1 +/- 2.4 vs. 2.7 +/- 3.6, p = NS). CONCLUSIONS: During coronary angioplasty, the cardiac pain experienced by patients is caused in part by stretching of the coronary artery wall. If the stretching is maintained at a constant level during repeated coronary occlusions, the cardiac pain is entirely predicted by the severity of myocardial ischemia and therefore does not appear to be directly modulated by the mechanisms responsible for the ischemic preconditioning.

Adenosine↗
PubMed1993

Transglutaminase covalently incorporates amines into human immunodeficiency virus envelope glycoprotein gp120 in vitro.

Human immunodeficiency virus envelope glycoprotein gp120, but not its precursor gp160, covalently incorporates both spermidine and glycine ethyl ester in the presence of Ca2+ and transglutaminase purified from guinea pig liver. The examined ability to act as enzyme substrate of various glutamine-containing gp120 fragments, including the principal neutralizing determinant, the CD4 binding domain, and the sequence 254-274, suggested to be involved in post-binding events and in virus entry in the host cell, indicated the glutamine-265 as possible reactive acyl donor site of the protein.

Amination↗
PubMed1992

Isolation and characterization of two binding proteins for advanced glycosylation end products from bovine lung which are present on the endothelial cell surface.

Nonenzymatic glycosylation of proteins, as occurs at an accelerated rate in diabetes, can lead to the formation of advanced glycosylation end products of proteins (AGEs), which can bind to endothelial cells, thereby altering cellular function in a manner which could contribute to the pathogenesis of diabetic angiopathy. In this report, we describe the isolation of two endothelial cell surface-associated proteins which mediate, at least in part, the interaction of AGEs with endothelium. Based on pilot studies demonstrating AGE binding activity with comparable characteristics in bovine endothelial cell and lung extracts, the material from lung was sequentially subjected to chromatography on hydroxylapatite, fast protein liquid chromatography Mono S, and gel filtration. Two distinct polypeptides, approximately 35 and approximately 80 kDa, were purified to homogeneity, each of which bound AGEs as demonstrated by competitive binding assays using cellular binding proteins immobilized on a plastic surface. NH2-terminal sequence analysis indicated that the approximately 35-kDa protein was novel, whereas the NH2-terminal sequence of the approximately 80-kDa protein was identical to that of lactoferrin. Immunocytologic studies using polyclonal antibody prepared to each of the purified polypeptides demonstrated the presence of immunoreactive material on the surface of bovine endothelial cells maintained under serum-free conditions. Furthermore, immunoelectron microscopic studies with antibodies to the approximately 35- and approximately 80-kDa AGE-binding proteins conjugated to different size colloidal gold particles confirmed the presence of the target antigens on the cell surface and suggested that they were closely associated. IgG purified from polyclonal antisera to either the 35- or 80-kDa AGE-binding proteins blocked the binding of 125I-AGE-albumin to the cell surface. These results indicate that endothelial cells express specific cell surface molecules which mediate AGE-endothelial interaction. These polypeptides represent a novel class of cell surface acceptor molecules for glucose-modified proteins which may promote degradation and/or transcytosis of the ligand, and modulation of cellular function.

Amino Acid Sequence↗
PubMed1991

Mass spectrometric identification of the amino donor and acceptor sites in a transglutaminase protein substrate secreted from rat seminal vesicles.

Four different transglutaminase-modified forms of a protein secreted by the rat seminal vesicles (SV-IV) were synthesized in vitro and characterized. FAB maps of both the native protein and its derivatives, produced by the purified guinea pig liver enzyme in the presence or absence of the polyamine spermidine, were obtained by mass spectrometric analysis after proteolytic digestions. Two differently derivatized SV-IV molecular forms, both possessing only one glutamine residue out of two (Gln-86) cross-linked to endogenous lysine residues, were produced when spermidine was omitted from the reaction mixture: (i) an insoluble homopolymer in which Lys-2, -4, -59, -78, -79, and -80 were involved in the linkage; (ii) a soluble form of the protein with an intramolecular epsilon-(gamma-glutamyl)lysine isopeptide bond between Gln-86 and Lys-59. Two species of SV-IV-spermidine adducts were obtained when the protein was treated with transglutaminase in the presence of high concentrations of the polyamine. The first one was characterized by one spermidine molecule covalently bound to Gln-86 and the second one by two spermidine molecules respectively bound to Gln-9 and Gln-86.

Amino Acid Sequence↗
PubMed1991

Endothelium and regulation of coagulation.

Endothelial cells form the luminal vascular surface and thus have a central role in the regulation of coagulation. One important way in which endothelial cells control the clotting system is by regulating the expression of binding sites for anticoagulant and procoagulant factors on the cell surface. In the quiescent state, endothelial cells maintain blood fluidity by promoting the activity of numerous anticoagulant pathways, including the protein C/protein S pathway. After activation, as can be brought about by cytokines, the balance of endothelial properties can be tipped to favor clot formation through coordinated induction of procoagulant and suppression of anticoagulant mechanisms. Tumor necrosis factor suppresses the endothelial anticoagulant cofactor thrombomodulin and induces expression of the procoagulant cofactor tissue factor. Working in concert, these changes can allow fibrin formation to proceed in an inflamed focus but maintain blood fluidity in the surrounding area of normal vasculature. Recent studies suggest that similar changes in endothelial coagulant properties can be induced by advanced glycosylation end products, proteins modified by glucose that accumulate in the vasculature at a rapid rate in diabetic subjects, indicating the potential relevance of these mechanisms in diabetic vascular disease.

Animals↗
PubMed1990

An anti-inflammatory protein secreted from the rat seminal vesicle epithelium inhibits the synthesis of platelet-activating factor and the release of arachidonic acid and prostacyclin.

Platelet-activating factor (PAF), a 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine, is a mediator of inflammation and endotoxic shock produced by a variety of stimulated cells. Since the main biosynthetic pathway of PAF involves acetylation of 1-O-alkyl-sn-glycero-3-phosphocholine (lyso-PAF) generated from 1-O-alkyl-2-acyl-sn-glycero-3-phosphocholine by phospholipase A2, we suggest a general physiological role played by steroid-induced anti-(phospholipase A2) proteins in the modulation of PAF synthesis. The results of the present study support this hypothesis since an androgen-induced anti-inflammatory protein, SV-IV, secreted from rat seminal vesicles, inhibits PAF synthesis in stimulated polymorphonuclear neutrophils, macrophages and endothelial cells. SV-IV impairs PAF synthesis by inhibiting the activation of phospholipase A2, that also results in the inhibition of arachidonic acid and prostacyclin release, and of acetyl-CoA:lyso-PAF acetyltransferase.

Acetyltransferases↗
PubMed1990

In vivo and in vitro inhibition of platelet aggregation by SV-IV, a major protein secreted from the rat seminal vesicle epithelium.

In summary, the present study documents that platelet aggregation triggered by thrombin, ADP, collagen and PAF both in vivo and in vitro, was prevented by SV-IV in a dose-dependent manner. Only platelet aggregation by AA was not affected by the protein, thus suggesting a possible involvement of PLA2 inhibition in the molecular mechanism at the basis of SV-IV anti-thrombotic effect.

Animals↗
PubMed1990

Acute increase in plasma osmolality as a cause of hyperkalemia in patients with renal failure.

These studies were performed in patients with chronic renal failure to understand the mechanism(s) of hyperkalemia secondary to hypertonic NaCl infusion. In 10 patients, after intravenous infusion of either 5% or 2.5% NaCl (6 mEq per kg body wt for 120 minutes in both solutions), the maximum increase in plasma potassium averaged 0.6 (range 0.3 to 1.3) mmol/liter (P less than 0.01) or 0.3 (range 0.2 to 0.6) mmol/liter (P less than 0.01), respectively. The rise of both plasma potassium and osmolality was significantly higher during 5% NaCl than during 2.5% NaCl infusion (P less than 0.01). A significant linear correlation (P less than 0.01) between plasma potassium and osmolality was observed. Urinary potassium excretion was increased to a similar extent by 5% NaCl and 2.5% NaCl infusion. The observed hyperkalemia, secondary to NaCl infusion, was independent of venous pH, plasma bicarbonate, anion gap, insulin levels, and urinary norepinephrine and epinephrine excretion, and was associated with a fall in plasma aldosterone concentration. In separate studies, nine patients were treated with desoxycorticosterone acetate (DOCA; 20 mg i.m. for three days) before receiving saline (5%) infusion. DOCA did not prevent the level increase in plasma potassium that remained significantly correlated with plasma osmolality (P less than 0.01). In conclusion, hypertonic NaCl infusion in patients with renal failure causes a clinically relevant hyperkalemia despite increased renal excretion of potassium. This hyperkalemia is independent of acid-base or hormonal mechanisms known to regulate extrarenal homeostasis of potassium, and is strictly correlated with a rise in plasma osmolality.

Acid-Base Equilibrium↗
PubMed1990

Transglutaminase-catalyzed modifications of SV-IV, a major protein secreted from the rat seminal vesicle epithelium.

One of the major proteins secreted from the rat seminal vesicle epithelium, namely SV-IV, was shown to act in vitro as acyl donor and acceptor substrate for transglutaminase from both guinea pig liver and rat anterior prostate secretory fluid. Electrophoretic and chromatographic experiments indicated that the enzyme catalyzed the formation of multiple modified forms of SV-IV. In the absence of small Mr amines, transglutaminase was able to produce at least six different molecular forms of the protein, half of which possessed an Mr higher than that of native SV-IV. These findings suggested that a variable number of intermolecular, and perhaps intramolecular, crosslinks were formed between one or both glutamine residues and one or more lysine residues occurring in the SV-IV polypeptide chain. In addition, at least three modified forms of the protein were produced by transglutaminase in the presence of high concentrations of spermidine, thus indicating the formation of different (gamma-glutamyl)polyamine derivatives of SV-IV. Rabbit uteroglobin and rat anterior prostate secretory protein(s) were also shown to be able to covalently bind spermidine in the presence of the enzyme. The possible biological significance of transglutaminase-mediated modifications of SV-IV, as well as of other proteins occurring in the mammal seminal fluid, are discussed.

Animals↗
PubMed1990

Modulation of endothelial hemostatic properties: an active role in the host response.

As the cells forming the luminal vascular surface, endothelium regulates both barrier function, and pro- and anticoagulant reactions. Endothelial cells can do this by controlling the expression of cell surface molecules, such as receptors that regulate the hemostatic balance and those that affect permeability across the endothelial monolayer. This regulation occurs in response to environmental stimuli, such as cytokines, which have a central role in inflammation, or glucose-modified proteins, which accumulate in the vasculature in aging and diabetes and are associated with vascular complications. The endothelial cell emerges as a dynamic regulator maintaining homeostasis in the quiescent state and contributing to the pathogenesis of vascular lesions in the stimulated state.

Animals↗
PubMed1990

Hypoxia modulates the barrier and coagulant function of cultured bovine endothelium. Increased monolayer permeability and induction of procoagulant properties.

Exposure of cultured endothelium to environments with low concentrations of oxygen, in the range of those observed in pathophysiologic hypoxemic states in vivo, compromises cellular barrier and coagulant function. An atmosphere with PO2 approximately 14 mm Hg was not lethally toxic to endothelial cultures, but cells became larger and exhibited small intercellular gaps. At low oxygen concentrations, passage of macromolecular tracers through hypoxic endothelial monolayers was accelerated in a time- and dose-dependent manner, presumably by a paracellular pathway via the gaps. Cell surface coagulant properties of the endothelium were also perturbed. At PO2 approximately 14 mm Hg thrombomodulin antigen and functional activity on the cell surface were diminished by 80-90%, and Northern blots demonstrated suppression of thrombomodulin mRNA. The decrease in thrombomodulin was twice as great compared with the general decline in total protein synthesis in hypoxia. In addition, expression of a direct Factor X activator developed under hypoxic conditions; the activator was membrane-associated and expressed on the surface of intact cultures, Ca-dependent, inhibited by HgCl2 but not PMSF, and had Km approximately 25 micrograms/ml for the substrate at pH 7.4. Synthesis of the activator was blocked by inclusion of cycloheximide, but not warfarin, in the culture medium. These results demonstrate that endothelial function is perturbed in a selective manner in the presence of low concentrations of oxygen, providing insights into mechanisms which may contribute to vascular dysfunction in hypoxemic states.

Animals↗
PubMed1990

[Cytomegalovirus and herpes simplex virus antibodies in patients with idiopathic ulcerative rectocolitis].

The total and fractioned titres of circulating anticytomegalovirus (CMV) and antiherpesvirus (HSV) antibodies were evaluated in 63 idiopathic ulcerative proctocolitis patients in follow-up. The population was disaggregated applying criteria related to the stage of the disease: duration, extension, number of observed relapses over the follow-up. It was noted that just the anti-HSV antibodies were correlated in a statistically significant way to the extension (p less than 0.025) and duration (p less than 0.025) of the disease. We believe that this behaviour is a manifestation of the disease and that the antiHSV titration may be included in a score of evaluation during the follow-up.

Adult↗