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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 (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 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. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted December 19, 2007 Accepted July 29, 2008 Resolution-phase macrophages possess a unique inflammatory phenotype that is controlled by cAMP Jonas Bystrom, Ian Evans, Justine Newson, Melanie Stables, Iqbal Toor, Nico van Rooijen, Mark Crawford, Paul Colville-Nash, Stuart Farrow, and Derek W. Gilroy* Centre for Clinical Pharmacology and Therapeutics, University College London, London, United Kingdom Centre for Cardiovascular Biology and Medicine, University College London, London, United Kingdom Department of Molecular Cell Biology, Faculty of Medicine, Vrije Universiteit, Amsterdam, Netherlands Centre for Molecular Medicine, Division of Medicine, University College London, London, United Kingdom Unit of Renal Medicine, St. Helier Hospital, London, United Kingdom Respiratory CEDD, GlaxoSmithKline, London, United Kingdom * Corresponding author; email: d.gilroy{at}ucl.ac.uk. Neutralising injurious stimuli, pro-inflammatory 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 post-inflammation tissue homeostasis with a role in controlling innate-immune mediated responses to secondary infection. However, while macrophages dominate resolution, their phenotype and role in restoring tissue physiology once inflammation abates is unknown. To address this, we isolated macrophages from the resolving phase of acute inflammation and found that compared to classically-activated pro-inflammatory M1 cells, resolution-phase macrophages (rM) 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 unique phenotype is controlled by cAMP, which, when inhibited, transforms rM to M1 cells. Conversely, elevating cAMP in M1 cells transforms them to rM with implications for cAMP in the resolution of systemic inflammation. It transpires that while rM are dispensable for clearing PMNs during self-limiting inflammation, they are essential for signalling post-resolution lymphocyte repopulation via COX 2 lipids. Thus, we describe rM macrophages as neither classically nor alternatively activated but a hybrid of both with a role in mediating post-resolution innate-lymphocyte repopulation and restoring tissue homeostasis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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