title: Extrinsic and intrinsic control of macrophage inflammatory responses.
abstract: Macrophages make major contributions to inflammatory immunopathology. In this work, we examine three disease scenarios, in which M1s play a major role early in the disease but eventually transitions into a population of cells with immunoregulatory activity. We propose that the transition from an inflammatory to a regulatory phenotype is a natural progression that regularly occurs in stimulated macrophages and that the timing of this transition is critical to maintaining homeostasis. In the first section of this review, we discuss the exogenous microenvironmental cues that may induce macrophages to enter a regulatory state. In the second half of this review, we discuss a novel mechanism, whereby TLR-stimulated macrophages can intrinsically induce their own regulatory activation state. They do so by secreting and synthesizing endogenous "reprogramming" signals that work in an autocrine fashion to promote a regulatory phenotype. We propose that these endogenous regulatory mechanisms exist to prevent macrophage-mediated immunopathology. Thus, macrophages can respond to endogenous and exogenous cues to regulate their activation state, and without these controlled regulatory responses, M1 would persist to the detriment of the host.
authors: 1.Rm. 3102, Bioscience Research Bldg., University of Maryland, College Park, MD 20742, USA. dmosser@umd.edu.
authors: Heather B
authors: HB
authors: Cohen
authors: David M
authors: DM
authors: Mosser
mesh_terms: D000818:Animals; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D009132:Muscles / Q000502:physiology; D018805:Sepsis / Q000276:immunology; D014945:Wound Healing
keywords: inflammation; pathology; regulation
references: Nat Cell Biol. 2010 Feb;12(2):153-63
references: 20081841
references: J Clin Invest. 1998 Feb 15;101(4):890-8
references: 9466984
references: Am J Respir Crit Care Med. 2000 Nov;162(5):1877-83
references: 11069829
references: J Immunol. 2009 Feb 15;182(4):2476-84
references: 19201903
references: Nature. 2006 Mar 9;440(7081):228-32
references: 16407890
references: PLoS One. 2010 May 21;5(5):e10763
references: 20505827
references: Semin Liver Dis. 2010 Aug;30(3):245-57
references: 20665377
references: J Clin Invest. 1939 May;18(3):291-300
references: 16694664
references: Biochem Biophys Res Commun. 1994 Aug 15;202(3):1688-96
references: 8060358
references: J Biol Chem. 2003 Apr 25;278(17):14677-87
references: 12590139
references: J Immunol. 2000 Aug 15;165(4):2134-41
references: 10925299
references: J Cell Biol. 2003 Dec 8;163(5):1133-43
references: 14662751
references: J Immunol. 2012 Oct 1;189(7):3669-80
references: 22933625
references: J Cell Sci. 2006 Jun 15;119(Pt 12):2497-507
references: 16720640
references: J Leukoc Biol. 2006 Dec;80(6):1298-307
references: 16905575
references: Sci Signal. 2010 Aug 17;3(135):ra62
references: 20716764
references: Eur J Immunol. 2011 Sep;41(9):2509-14
references: 21952807
references: Muscle Nerve. 1997 Feb;20(2):158-66
references: 9040653
references: Am J Pathol. 2009 Jul;175(1):132-47
references: 19528348
references: J Immunol. 1996 Nov 15;157(10):4634-40
references: 8906843
references: J Immunol. 2011 Nov 15;187(10):5408-18
references: 22013115
references: Blood. 2013 Sep 12;122(11):1935-45
references: 23908469
references: J Cell Biol. 2011 Oct 17;195(2):307-22
references: 21987635
references: FEBS J. 2013 Sep;280(17):4118-30
references: 23384231
references: Am J Physiol Regul Integr Comp Physiol. 2010 Sep;299(3):R832-42
references: 20631294
references: Front Immunol. 2011 Nov 16;2:62
references: 22566851
references: J Immunol. 2005 Jul 1;175(1):469-77
references: 15972681
references: J Exp Med. 1992 Jul 1;176(1):287-92
references: 1613462
references: J Pharm Pharmacol. 1966 Mar;18(3):199-200
references: 4381222
references: J Anat. 1996 Feb;188 ( Pt 1):17-28
references: 8655404
references: J Biol Chem. 2009 Dec 11;284(50):34490-505
references: 19822518
references: Nat Rev Immunol. 2008 Dec;8(12):958-69
references: 19029990
references: FASEB J. 2011 Jan;25(1):358-69
references: 20889618
references: Am J Physiol Regul Integr Comp Physiol. 2006 Jun;290(6):R1488-95
references: 16424086
references: Eur J Immunol. 2012 Jul;42(7):1804-14
references: 22585447
references: J Immunol. 2010 Jul 1;185(1):605-14
references: 20498354
references: Eur J Immunol. 2008 Jun;38(6):1610-20
references: 18465770
references: J Immunol. 1997 Aug 1;159(3):1451-8
references: 9233643
references: Infect Immun. 1988 May;56(5):1352-7
references: 3356468
references: Annu Rev Pathol. 2011;6:19-48
references: 20887193
references: Immunol Res. 2012 Sep;53(1-3):11-24
references: 22418728
references: J Cell Mol Med. 2009 Sep;13(9B):3485-96
references: 19228260
references: Am J Physiol Regul Integr Comp Physiol. 2010 May;298(5):R1173-87
references: 20219869
references: Immunity. 2010 May 28;32(5):593-604
references: 20510870
references: Am J Pathol. 2009 Dec;175(6):2518-27
references: 19893053
references: J Immunol. 2009 Feb 15;182(4):1929-39
references: 19201846
references: EMBO J. 2006 Nov 1;25(21):5071-82
references: 17036048
references: J Exp Med. 1994 Dec 1;180(6):2365-70
references: 7525853
references: Hum Mol Genet. 2009 Feb 1;18(3):482-96
references: 18996917
references: J Cell Biochem. 2013 Jan;114(1):220-9
references: 22903635
references: Curr Top Dev Biol. 2011;96:139-65
references: 21621070
references: Trends Immunol. 2009 Oct;30(10):475-87
references: 19781994
references: Development. 2000 Jun;127(11):2269-82
references: 10804170
references: BMC Genomics. 2010 Nov 24;11:659
references: 21106073
references: Cell. 2003 Mar 7;112(5):645-57
references: 12628185
references: Acta Anat (Basel). 1991;140(3):201-12
references: 1714222
references: J Exp Med. 2007 May 14;204(5):1057-69
references: 17485518
references: J Exp Med. 2012 Mar 12;209(3):551-63
references: 22370717