Senescent human neutrophils undergo programmed cell death (apoptosis), leading to their recognition and phagocytosis by mature macrophages. At inflamed sites in vivo these processes may represent a neutrophil removal mechanism with the potential to limit the histotoxic capacity of these cells. Phagocytosis can provoke marked proinflammatory responses by macrophages. A macrophage proinflammatory response to the ingestion of apoptotic neutrophils would limit the efficacy of this neutrophil removal mechanism as a component of inflammatory resolution. In the present study we examined two macrophage proinflammatory responses; secretion of the granule enzyme N-acetyl-beta-D-glucosaminidase (NAG) and release of the membrane lipid-derived inflammatory mediator thromboxane A2 (TxA2, measured as TxB2). By contrast with the marked release of NAG and TxB2 elicited by phagocytosis of control particles (opsonised zymosan and immunoglobulin G-coated erythrocytes), macrophage ingestion of apoptotic neutrophils resulted in minimal release of NAG and no release of TxB2; indeed, there was a small depression of TxB2 release that was not due to a toxic effect of neutrophil uptake because macrophages ingesting apoptotic neutrophils retained marked TxB2 responses to subsequent stimulation with opsonised zymosan. Furthermore, there was significant TxB2 release in response to macrophage phagocytosis of apoptotic neutrophils that had been coated with opsonic serum, demonstrating that the lack of macrophage response was determined by the mechanism of recognition rather than the properties of the apoptotic particle itself. These observations are consistent with the hypothesis that macrophage clearance of senscent neutrophils undergoing apoptosis is an injury-limiting mechanism that favors resolution rather than persistence of the inflammatory response and are consistent with observations that the waves of apoptotic cell removal seen in embryological removal and thymic involution do not trigger an inflammatory response.
Abstract We have previously reported that human airway macrophages do not respond to the β-adrenoceptor agonist isoprenaline. The airway macrophage is known to be derived from the blood monocyte. In this study we have assessed the effect of β-adrenoceptor stimulation on human monocytes matured into macrophages in vitro, to determine whether the lack of response previously observed in the airway macrophage may be a consequence of differentiation. The release of thromboxane B2 (TXB2) from freshly isolated monocytes stimulated by opsonized zymosan (OPZ) was inhibited by 39.3 ± 5.5% in the presence of isoprenaline (10-7 M). However, the response was lost in the monocyte-derived macrophage (MDM), where isoprenaline (10-7 M) caused only 4.0 ± 9.3% inhibition of OPZ-stimulated TXB2 release. In contrast forskolin (10-5 M) inhibited MDM TXB2 release by 36.4 ± 17.3%, indicating that the adenylyl cyclase was functional. Measurement of adenylyl cyclase activity showed that there was a reduction in the basal level, 17.03 ± 4.1 to 7.9 ± 4.6 cyclic AMP pmol/min/mg protein, and NaF (10-2 M)-induced activity, 116.3 ± 32.1 to 21.9 ± 12.6 cyclic AMP pmol/min/mg protein, between freshly isolated monocytes and MDMs, respectively. In addition, there was no change in MDM basal adenylyl cyclase activity on exposure to isoprenaline. Thus we have demonstrated the loss of β-adrenoceptor function during the maturation of human monocytes to macrophages in vitro, despite a functional adenylyl cyclase system. In this respect the monocyte-derived macrophage is like the airway macrophage. J. Leukoc. Biol. 57: 395–400; 1995.
Abstract Die cyclischen Harnstoffe (III) werden zu den Verbindungen (IV) silyliert, die ohne Isolierung in Gegenwart eines Quecksilberkatalysators mit dem aus (I) zugänglichen Bromid (II) in die Nucleoside (V) übergeführt werden.
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of 3-deazaneplanocin A, a powerful inhibitor of S-adenosylhomocysteine hydrolase with potent and selective in vitro and in vivo antiviral activitiesChristopher K. H. Tseng, Victor E. Marquez, Richard W. Fuller, Barry M. Goldstein, David R. Haines, Howard McPherson, Jack L. Parsons, William M. Shannon, Gussie Arnett, and Cite this: J. Med. Chem. 1989, 32, 7, 1442–1446Publication Date (Print):July 1, 1989Publication History Published online1 May 2002Published inissue 1 July 1989https://pubs.acs.org/doi/10.1021/jm00127a007https://doi.org/10.1021/jm00127a007research-articleACS PublicationsRequest reuse permissionsArticle Views875Altmetric-Citations91LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
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