Polyvinyl Sponge Implants Research Articles

Accumulation of tolerogenic cells at the site of granulomatous foreign-body reaction

Event Abstract Back to Event Accumulation of tolerogenic cells at the site of granulomatous foreign-body reaction Dragana Vucevic1, 2*, Sasa Vasilijic1, 2, Jelena Djokic1, Biljana Bozic3, Ivana Majstorovic1, Sergej Tomic2, Milijana Vasiljevska1, Biljana Draskovic-Pavlovic1, 2 and Miodrag Colic2 1 Institute for Medical Research Military Medical Academy, Serbia 2 Medical Faculty of the Military Medical Academy, University of Defense, Serbia 3 Faculty of Biology, Institute for Physiology and Biochemistry, Serbia The granulomatous foreign-body reaction (GFBR) is a special type of chronic inflammation characterised by infiltration of inflammatory cells (ICs). Using a model of subcutaneous implantation of polyvinyl sponges in rats, we studied the phenotypic and functional characteristics of these cells, with particular reference to the properties of antigen presenting cells and lymphocytes. ICs were isolated from sponge exudates at days 1-21 after implantation. Dendritic cells (DCs) and lymphocytes were purified using a combination of separation gradients, adherence to plastics, and immunomagnetic sorting. We showed that dominant population of ICs at day 1 and 3 were granulocytes, followed by their decrease thereafter. The number of mononuclear cells (MNCs), macrophages and DCs, progressively increased after day 3, reaching maximal values at day 7. Maximal number of lymphocytes was detected at day 10. In addition, total ICs isolated from day 7 till day 10 exerted significant suppressive activity in co-culture with autologous ConA-stimulated thymocytes and alogeneic lymph node T cells. This finding correlated with the increased level of IL-10 in culture supernatants and the increased proportion MHC class II+ IDO+ DCs and CD3+ CD25+ Foxp3+ lymphocytes at day 7 and day 10, respectively. We did not find any significant difference in the number of these cell populations between regional lymph nodes MNCs and peripheral blood MNCs of experimental animals compared to controls. In conclusion, accumulation of cells with tolerogenic characteristics in GFBR might be relevant for the suppression of inflammation and the prevention of unwanted immune response. Keywords: granulomatous foreign-body reaction, Dendritic Cells, regulatory T cells, Lymph Node, chronic inflammation Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Adaptive Immunity Citation: Vucevic D, Vasilijic S, Djokic J, Bozic B, Majstorovic I, Tomic S, Vasiljevska M, Draskovic-Pavlovic B and Colic M (2013). Accumulation of tolerogenic cells at the site of granulomatous foreign-body reaction. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00029 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 08 Mar 2013; Published Online: 22 Aug 2013. * Correspondence: Prof. Dragana Vucevic, Institute for Medical Research Military Medical Academy, Belgrade, Serbia, draganavucevic@yahoo.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Dragana Vucevic Sasa Vasilijic Jelena Djokic Biljana Bozic Ivana Majstorovic Sergej Tomic Milijana Vasiljevska Biljana Draskovic-Pavlovic Miodrag Colic Google Dragana Vucevic Sasa Vasilijic Jelena Djokic Biljana Bozic Ivana Majstorovic Sergej Tomic Milijana Vasiljevska Biljana Draskovic-Pavlovic Miodrag Colic Google Scholar Dragana Vucevic Sasa Vasilijic Jelena Djokic Biljana Bozic Ivana Majstorovic Sergej Tomic Milijana Vasiljevska Biljana Draskovic-Pavlovic Miodrag Colic PubMed Dragana Vucevic Sasa Vasilijic Jelena Djokic Biljana Bozic Ivana Majstorovic Sergej Tomic Milijana Vasiljevska Biljana Draskovic-Pavlovic Miodrag Colic Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Prostaglandins and the anti-inflammatory activities of aspirin and sodium salicylate

Acetylsalicylic acid (aspirin) and sodium salicylate are equally effective in reducing the swelling in the carrageenan-induced paw test and the accumulation of leucocytes into the inflammatory exudate produced by the subcutaneous implantation of polyvinyl sponges in the rat. Aspirin but not sodium salicylate caused a significant reduction in the potentiation of paw oedema found after the concurrent administration of carrageenan and arachidonic acid. Some implications of these findings are discussed.

Effects of a human plasma fraction on leucocyte migration into inflammatory exudates

A fraction prepared from normal human plasma inhibits the migration of polymorphonuclear and mononuclear leucocytes into inflammatory exudates produced by the intrapleural injection of carrageeman or turpentine by the subcutaneous implantation of polyvinyl sponges in the rat. The mechanism of the effect does not involve complement depletion.

Increased nitric oxide formation followed by increased arginase activity induces relative lack of arginine at the wound site and alters whole nutritional status in rats almost within the early healing period

Nitric oxide (NO) production and free amino acid fluxes at the wound side during the first 3 days following cutaneous wound were investigated. Experiments were performed on Albino Oxford rats ( n = 18) underwent cutaneous implantation of polyvinyl sponges. Intact animals ( n = 6) were controls. Nitrites, nitrates, free amino acids and urea were measured both in plasma and wound fluids. Inducible nitric oxide synthase (iNOS) gene expressions at wound site were analyzed, too. The highest levels of both iNOS gene expression and its activity (increased wound fluid citrulline and nitrites) were at the first day. Wound fluid nitrates were significantly above plasma levels throughout the whole period, while molar nitrate to nitrite ratio steadily increased. It was associated with gradual increase of both ornithine and urea as well as steadily decreases of arginine and increases of phenylalanine at the wound site. Gradual decrease in glycine to branched-chain molar ratio was observed both in plasma and wound fluids. In conclusion, an early locally induced alterations in Arg metabolism, due to increased NO formation followed by increased arginase activity, produces relative lack of Arg at the wound site and disturbs nutritional status of the whole body almost within early healing period following cutaneous wound in rats. It is likely that NO autoxidation at the wound side is influenced by substrate availability.

Dendritic cells acquire tolerogenic properties at the site of sterile granulomatous inflammation

Subcutaneous implantation of polyvinyl sponges represents a suitable model for studying the mechanisms of acute and chronic inflammation, granulomatous foreign-body reaction, as well as wound healing. Using such a model in rats, we studied the phenotypic and functional characteristics of dendritic cells (DC). DC were purified from the sponge exudate using a combination of separation gradients, adherence to plastics, and immunomagnetic sorting. We have shown that the number of DC progressively increased in the sponges, reaching maximal values at day 10 after implantation, followed by their decrease thereafter. Inflammatory DC expressed MHC class II molecules and myeloid markers CD11b, CD11c, and CD68. A subset of DC expressed CD4, R-MC46, DEC-205, R-MC17, and CCR1. Compared to DC isolated in the early phase of inflammation (day 6 DC), DC in the late stage of inflammation (day 14 DC) had a lower capability to stimulate the proliferation of allogeneic lymphocytes and CD4+ T cells. This finding correlated with the downregulation of CD80, CD86, and CD54 expression and the increased proportion of plasmacytoid MHC class II+ His 24+ His 48+ DC. The suppression of allogeneic lymphocyte proliferation was abrogated by the treatment of DC with lipopolysaccharide. In addition, day 14 DC exerted tolerogenic capability in co-culture with allogenic CD4+ T cells. These results correlated with the increased levels of IL-10 and TGF-β in culture supernatants and the sponge exudate.

Neutropenia, Inflammation, and the Kinetics of Transfused Neutrophils in Rabbits

A rabbit model was used to study the effects of neutropenia and inflammation on the intravascular distribution, survival, and tissue accumulation of transfused neutrophils. Donor blood labeled with [(3)H]thymidine was infused into normal or neutropenic (vinblastine treated) animals. Inflammation was created by subcutaneous implantation of polyvinyl sponges, some with added endotoxin. Initial circulating neutrophil pool recovery, survival, and inflammatory site accumulation of labeled neutrophils were measured. Neutropenia was associated with a relative increase in the marginal pool size, manifested by a diminished initial circulating pool (CNP) recovery of transfused cells. The CNP recovery was directly proportional to recipient neutrophil count. Neutropenia had no effect on the intravascular survival of transfused cells and was accompanied by only a modest decrease in the inflammatory site recovery of the transfused neutrophils (10.4+/-5.4 vs. 14.4+/-4.0% in normals). Inflammation in the form of subcutaneous polyvinyl sponges was accompanied by an increase in margination with initial CNP recoveries of 24.3+/-4.7 and 27.6+/-8.8% at zero and 4 h after implantation respectively (normal, 38.2+/-9.9%). Transit through the CNP was hastened by inflammation with a t((1/2)) of 2.02+/-0.72 h (normal, 3.2+/-1.0 h). Addition of endotoxin to the sponges further perturbed cell kinetics. CNP recoveries were considerably lower and half-lifes were initially shorter and subsequently uninterpretable in studies done after endotoxin sponge insertion. Inflammatory site accumulation was markedly diminished to 7.4+/-1.9% of injected neutrophil label in the endotoxin sponge animals, suggesting that many of the transfused cells were functionally unavailable rather than marginated. These studies demonstrate that neutropenia and inflammation with or without endotoxin markedly alter the kinetics of transfused neutrophils and that CNP recovery of transfused cells is not necessarily predictive of their inflammatory site accumulation.

An enzyme histochemical study of the effect of various concentrations of formocresol on connective tissues

A histochemical profile of selected enzyme activities has been assessed in connective tissue cells of polyvinyl sponge implants in the absence or presence of various dilutions of formocresol. The effects of formocresol are more severe among cells receiving the higher concentrations. Little difference is noted between the full concentration of formocresol and a 1 5 dilution in terms of initial effects of tissue fixation. Thus, it is concluded that a 1 5 dilution may be as effective as the full concentration and, at the same time, may provide a faster recovery from the cytotoxic effects of formocresol.

Effects of very large doses of penicillin G given orally to rats.

Nimni and Bavetta1 reported a connective tissue disorder in rats fed penicillamine. The disorder was reflected by decreased breaking strength of unwounded and wounded skin, decreased collagen synthesis in polyvinyl sponge implants and a diminished proportion of insoluble to soluble collagen in such granulomas. We have studied this phenomenon in rats and guinea-pigs2–4 and have likened it to the lathyritic state induced by feeding β-amino propionitrile, a view also expressed by Nimni5. Penicillamine can be derived6 from both the in vitro and the in vivo hydrolysis of penicillin, so we set out to determine whether the feeding of very large doses of penicillin would cause a collagen defect similar to that caused by penicillamine.

The metabolism of mucopolysaccharides. 3. The effect of adrenocortical hormones on enzymes involved in glucuronide synthesis and metabolism in connective tissue.

The levels of activity of hexokinase, phosphoglucomutase, uridine diphosphoglucose pyrophosphorylase, and uridine diphosphoglucose dehydrogenase, which are involved in the synthesis of glucuronic acid, and the levels of glucuronosyltransferase and β-glucuronidase, which are involved in its metabolism, were studied in connective tissue from polyvinyl sponge implants from sham-operated and adrenalectomized rats which had received "replacement therapy" of individual steroids.The levels of activity of these enzymes were significantly increased in sham-operated rats which had been treated with corticosterone, cortisone, or hydrocortisone. In adrenalectomized animals, the increased or decreased enzyme activities were restored to normal levels by "therapy" with corticosterone, cortisone, or hydrocortisone. In some cases there was an over-correction at the particular level of hormone treatment. In both sham-operated and adrenalectomized animals, treatment with deoxycorticosterone, progesterone, or Reichstein's substance S frequently, but not always, resulted in little or no change in activity of the enzymes.

Polyvinyl sponge implants: Experimental and clinical observations

Summary Experiments are reported which prove that polyvinyl sponge when implanted subcutaneously in rats may eventually give rise to a local sarcoma. The degree of carcinogenicity of this plastic depends on the size and thickness of the implanted sponge. Eight polyvinyl sponge implants have also been examined microscopically after their removal from human patients and the histology compared with that of plastic sponge implanted subcutaneously in rats. The question is discussed as to whether or not this proved carcinogenicity for laboratory animals implies that there may be some danger of human cancer following the implantation of pieces of polyvinyl sponge.

Polyvinyl sponge implants: Experimental and clinical observations

Summary Experiments are reported which prove that polyvinyl sponge when implanted subcutaneously in rats may eventually give rise to a local sarcoma. The degree of carcinogenicity of this plastic depends on the size and thickness of the implanted sponge. Eight polyvinyl sponge implants have also been examined microscopically after their removal from human patients and the histology compared with that of plastic sponge implanted subcutaneously in rats. The question is discussed as to whether or not this proved carcinogenicity for laboratory animals implies that there may be some danger of human cancer following the implantation of pieces of polyvinyl sponge.

Connective tissue development in subcutaneously implanted polyvinyl sponge: II. Enzymic changes during development

The changes in enzyme activity that accompany connective tissue development in polyvinyl sponge implants in female rats have been measured quantitatively. The enzyme activities are grouped into three general developmental patterns, which are related to processes of cell proliferation, tissue maturation, and collagen synthesis and degradation. Glutamic oxalacetic transaminase, imidodipeptidase. iminodipeptidase, catalase, cytochrome c reductase and phenolsulfatase activities develop in parallel with deoxyribonucleic acid (DNA) and then remain at a relatively constant level during the remainder of tissue development. Proteinase ( pH 3.2), acid phosphalase, and β-glucuronidase activities continue to increase when the DNA and collagen content have reached their maximum levels. Alkaline phosphatase, peroxidase, lactic dehydrogenase, and malic dehydrogenase activities pass through a maximum and then decline before, or at the same time. DNA reaches its maximum.

Connective tissue development in subcutaneously implanted polyvinyl sponge: I. Biochemical changes during development

The changes in wet weight, soluble protein, deoxyribonucleic acid (DNA), collagen, free hydroxyproline, and ascorbic acid have been measured during the process of connective tissue development in polyvinyl sponge implants in the female rat. There was a continual decrease in tissue wet weight during the first 20 days after sponge implantation, accompanied by a reduction in the sponge volume. The amount of soluble proteins per gram of implanted sponge remained constant throughout the period of development. Deoxyribonucleic acid increased to a maximum at 20 days and then remained relatively constant. Ascorbic acid was present initially in high concentration in the extracellular fluid and underwent further increases in parallel with DNA. Collagen accumulation reached a maximum by 36 days. Free hydroxyproline paralleled the appearance of DNA. No relationship could be established between free hydroxyproline and collagen synthesis or degradation.

Pathogenesis of the collagen defect in experimental scurvy.

In the quarter century since Wolbach's studies 1 on the disturbance in collagen formation in experimental scorbutus, extensive research has been performed in this field. Much of it was stimulated by the hope that manipulation of the collagen defect might provide a lead to better understanding of collagen metabolism, wound healing, and the collagen diseases. In 1956, Dunphy and his associates 2 reported on a preliminary trial of polyvinyl sponge implants into the abdominal wall of experimental animals in this field. Others 3,4 had used this material previously but not in experimental scurvy. The technique has certain advantages over experimental linear or excised wounds in studies of reparative collagen deposition. For example, with multiple implants in the same animal one sponge can be submitted for chemical analysis and the other for pathologic evaluation. Our experience with the simultaneous implantation of polyvinyl sponges into the abdominal wall and anterior chamber of