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Blood, 15 November 2008, Vol. 112, No. 10, pp. 4117-4127. Prepublished online as a Blood First Edition Paper on September 8, 2008; DOI 10.1182/blood-2007-12-129767. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2007-12-129767v1 112/10/4117    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Bystrom, J. Articles by Gilroy, D. W. Search for Related Content PubMed PubMed Citation Articles by Bystrom, J. Articles by Gilroy, D. W. Related Collections Immunobiology Phagocytes Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Resolution-phase macrophages possess a unique inflammatory phenotype that is controlled by cAMP Jonas Bystrom1, Ian Evans2, Justine Newson1, Melanie Stables1, Iqbal Toor1, Nico van Rooijen3, Mark Crawford4, Paul Colville-Nash5, Stuart Farrow6, and Derek W. Gilroy1 1 Centre for Clinical Pharmacology and Therapeutics and 2 Centre for Cardiovascular Biology and Medicine, Division of Medicine, University College London, London, United Kingdom; 3 Department of Molecular Cell Biology, Vrije Universiteit, VUMC, Amsterdam, The Netherlands; 4 Centre for Molecular Medicine, Division of Medicine, University College London, London, United Kingdom; 5 St Helier Hospital, Carshalton, Surrey, United Kingdom; and 6 Respiratory Centre of Excellence in Drug Discovery, GlaxoSmithKline, Stevenage, United Kingdom Neutralizing injurious stimuli, proinflammatory mediator catabolism, and polymorphonuclear leukocyte (PMN) clearance are determinants of inflammatory resolution. To this, we recently added innate-type lymphocyte repopulation as being central for restoring postinflammation tissue homeostasis with a role in controlling innate immune–mediated responses to secondary infection. However, although macrophages dominate resolution, their phenotype and role in restoring tissue physiology once inflammation abates are unknown. Therefore, we isolated macrophages from the resolving phase of acute inflammation and found that compared with classically activated proinflammatory M1 cells, resolution-phase macrophages (rMs) possess weaker bactericidal properties and express an alternatively activated phenotype but with elevated markers of M1 cells including inducible cyclooxygenase (COX 2) and nitric oxide synthase (iNOS). This phenotype is controlled by cAMP, which, when inhibited, transforms rM to M1 cells. Conversely, elevating cAMP in M1 cells transforms them to rMs, with implications for cAMP in the resolution of systemic inflammation. It transpires that although rMs are dispensable for clearing PMNs during self-limiting inflammation, they are essential for signaling postresolution lymphocyte repopulation via COX 2 lipids. Thus, rM macrophages are neither classically nor alternatively activated but a hybrid of both, with a role in mediating postresolution innate-lymphocyte repopulation and restoring tissue homeostasis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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