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      Hemoperfusion with an Immobilized Polymyxin B Column Reduces the Blood Level of Neutrophil Elastase

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          Abstract

          Background: We investigated whether direct hemoperfusion with an immobilized polymyxin B column (DHP with PMX) could reduce the blood level of neutrophil elastase. Methods: 20 sepsis patients were enrolled in the study. DHP with PMX was performed twice within a 24-hour period. Neutrophil elastase was measured 7 times. Results: Neutrophil elastase was 468 ± 75.1 µg/l, while it was 1,531 ± 201.7 µg/l immediately after the first session, declined to 351 ± 73.9 µg/l before the second session of DHP with PMX, and increased again to 599.3 ± 112.7 µg/l immediately after the second session, 328 ± 73.7 µg/l at 24 h, 264 ± 39.3 µg/l at 48 h, and 230 ± 36.1 µg/l at 72 h after DHP with PMX. The levels from 48 h onwards were significantly lower compared with that before treatment. Conclusion: DHP with PMX has an overall effect that reduces circulating neutrophil elastase levels.

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          Most cited references13

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          Phagocytosing neutrophils produce and release high amounts of the neutrophil-activating peptide 1/interleukin 8

          After phagocytosis of yeast opsonized with IgG, neutrophil leukocytes (polymorphonuclear leukocytes [PMN]) expressed high levels of neutrophil-activating peptide 1/interleukin 8 (NAP-1/IL-8) mRNA, which peaked after 3-5 h and were still elevated after 18 h. A similar but quantitatively less prominent effect was obtained with lipopolysaccharide (LPS). After phagocytosis, but not after exposure to LPS, the PMN progressively released considerable amounts of NAP-1/IL-8 into the culture medium (18.6-50 ng/ml in 18 h). The peptide released was biologically active, as indicated by the transient elevation of cytosolic-free calcium in PMN exposed to aliquots of the culture supernatants, and desensitization by prestimulation of the cells with recombinant NAP-1/IL-8. By producing NAP-1/IL-8 at sites where they phagocytose invading microorganisms, PMN could enhance the recruitment of new defense cells.
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            Circulating human peripheral blood granulocytes synthesize and secrete tumor necrosis factor alpha.

            Circulating peripheral blood polymorphonuclear neutrophils (PMNs) have long been considered terminally differentiated cells that do not synthesize or secrete protein. However, work of others and ourselves has shown that PMNs can secrete the cytokine interleukin 1. In the present study we investigated whether circulating PMNs are capable of synthesizing and secreting another cytokine, tumor necrosis factor alpha (TNF-alpha). Highly purified (greater than 99% granulocytes) PMNs were isolated from normal human volunteer blood and cultured with or without bacterial lipopolysaccharide (LPS) for up to 24 hr. Cell culture supernatants were collected and tested for TNF-alpha, and total RNA was isolated from cells at various times after stimulation and assessed for TNF-alpha mRNA by Northern blot techniques. The results showed that message for TNF-alpha was produced after 60 min of in vitro stimulation with LPS and was maximal at about 4 hr. TNF-alpha was secreted into the supernatant of unstimulated PMNs from two different donors during 24 hr of culture (35-50 pg/ml), but significantly more (160-190 pg/ml) was secreted by PMNs when stimulated with LPS. PMNs from six other normal volunteers showed significant LPS-stimulated secretion of TNF at 60-180 min of culture. The secreted product also had biological activity against the TNF-sensitive L-M cell line, confirming that PMNs can make and secrete immunologically and biologically active TNF. Since it is also possible for monocytes to synthesize and secrete TNF, the amount of TNF secreted by a monocyte population equal to 20% of the PMNs cultured was measured. The results showed that monocytes at a concentration 20 times that potentially contaminating the PMN populations cultured could not produce as much TNF (unstimulated, 26-65 pg/ml; stimulated, 32-87 pg/ml). The PMN must now be considered a cell capable of altering the acute inflammatory response and modulating the immune response through the synthesis and release of cytokines.
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              Elastase in tissue injury.

              A Janoff (1984)
              This article surveys elastinolytic proteinases in man, excluding enzymes of the pancreas and digestive tract. Special emphasis is placed on the elastase of polymorphonuclear neutrophils (PMN). The properties of this latter enzyme, its target molecules in plasma and connective tissues, and its endogenous regulators are briefly discussed. Persistent activity of the enzyme, even in the presence of its regulatory inhibitors, is explained. The chapter closes with a brief discussion of several pulmonary diseases in which elastase-mediated tissue injury is thought to play a role.
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                Author and article information

                Journal
                BPU
                Blood Purif
                10.1159/issn.0253-5068
                Blood Purification
                S. Karger AG
                0253-5068
                1421-9735
                2006
                February 2006
                15 February 2006
                : 24
                : 2
                : 212-217
                Affiliations
                aDepartment of Emergency and Critical Care Medicine, Nihon University School of Medicine and bDepartment of Clinical Engineering, Surugadai Nihon University Hospital, Tokyo, Japan
                Article
                90593 Blood Purif 2006;24:212–217
                10.1159/000090593
                16391471
                d919b70d-319e-4ee0-9162-8c7085760185
                © 2006 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                : 21 October 2005
                Page count
                Figures: 1, Tables: 4, References: 23, Pages: 6
                Categories
                Original Paper

                Cardiovascular Medicine,Nephrology
                Systemic inflammatory response syndrome,Immobilized polymyxin B fiber column,Neutrophil elastase,Direct hemoperfusion,Sepsis

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