title: On the Functional Overlap between Complement and Anti-Microbial Peptides.
abstract: Intriguingly, activated complement and anti-microbial peptides share certain functionalities; lytic, phagocytic, and chemo-attractant activities and each may, in addition, exert cell instructive roles. Each has been shown to have distinct LPS detoxifying activity and may play a role in the development of endotoxin tolerance. In search of the origin of complement, a functional homolog of complement C3 involved in opsonization has been identified in horseshoe crabs. Horseshoe crabs possess anti-microbial peptides able to bind to acyl chains or phosphate groups/saccharides of endotoxin, LPS. Complement activity as a whole is detectable in marine invertebrates. These are also a source of anti-microbial peptides with potential pharmaceutical applicability. Investigating the locality for the production of complement pathway proteins and their role in modulating cellular immune responses are emerging fields. The significance of local synthesis of complement components is becoming clearer from in vivo studies of parenchymatous disease involving specifically generated, complement-deficient mouse lines. Complement C3 is a central component of complement activation. Its provision by cells of the myeloid lineage varies. Their effector functions in turn are increased in the presence of anti-microbial peptides. This may point to a potentiating range of activities, which should serve the maintenance of health but may also cause disease. Because of the therapeutic implications, this review will consider closely studies dealing with complement activation and anti-microbial peptide activity in acute inflammation (e.g., dialysis-related peritonitis, appendicitis, and ischemia).
authors: Department of Infectious Diseases - Medical Microbiology and Hygiene, Ruprecht-Karls-University of Heidelberg , Heidelberg , Germany.
authors: Jana
authors: J
authors: Zimmer
authors: Department of Academic Endocrinology, Diabetes and Metabolism, Hull York Medical School, University of Hull , Hull , UK.
authors: James
authors: J
authors: Hobkirk
authors: Department of Infection, Immunity and Inflammation, University of Leicester , Leicester , UK.
authors: Fatima
authors: F
authors: Mohamed
authors: Department of Infection, Immunity and Inflammation, University of Leicester , Leicester , UK ; Department of Immunology, Leicester Royal Infirmary , Leicester , UK.
authors: Michael J
authors: MJ
authors: Browning
authors: Department of Infection, Immunity and Inflammation, University of Leicester , Leicester , UK.
authors: Cordula M
authors: CM
authors: Stover
keywords: acute inflammation; deficiencies; histidine tag; immune cells; innate immunity
references: Clin Dev Immunol. 2012;2012:407324
references: 23049598
references: J Immunol. 1996 Jun 1;156(11):4429-34
references: 8666817
references: J Biol Chem. 2011 May 20;286(20):17585-92
references: 21454577
references: Kidney Int. 2000 Oct;58(4):1580-7
references: 11012892
references: Immunology. 1983 May;49(1):169-74
references: 6840804
references: Front Immunol. 2012 Mar 05;3:38
references: 22566921
references: PLoS One. 2012;7(10):e46476
references: 23077510
references: J Innate Immun. 2014;6(4):530-41
references: 24556597
references: Mol Immunol. 1999 Dec;36(18):1235-47
references: 10684963
references: Curr Opin Gastroenterol. 2006 Nov;22(6):644-50
references: 17053443
references: Semin Immunol. 2007 Apr;19(2):70-83
references: 17485224
references: Crit Rev Biotechnol. 2012 Jun;32(2):143-71
references: 22074402
references: Crit Care. 2007;11(1):R19
references: 17302973
references: J Immunol. 1988 May 1;140(9):3082-5
references: 2834451
references: Med Microbiol Immunol. 2014 Aug;203(4):257-71
references: 24728387
references: Immunol Res. 2005;33(2):103-12
references: 16234578
references: J Leukoc Biol. 2014 Jun;95(6):971-81
references: 24550523
references: Infect Immun. 2006 Sep;74(9):5284-91
references: 16926422
references: J Biol Chem. 2014 Aug 15;289(33):22969-79
references: 24970887
references: Methods Mol Biol. 2010;618:137-54
references: 20094863
references: Annu Rev Immunol. 1986;4:503-28
references: 3518749
references: Cell Immunol. 1985 Feb;90(2):339-57
references: 3967303
references: Blood. 2011 Jan 27;117(4):1340-9
references: 21063021
references: Innate Immun. 2015 Jan;21(1):30-41
references: 24336024
references: PLoS One. 2011;6(5):e20036
references: 21625439
references: J Innate Immun. 2012;4(3):284-92
references: 22261275
references: Biochem Biophys Res Commun. 1993 Nov 30;197(1):351-2
references: 8250944
references: N Engl J Med. 2003 Jan 9;348(2):167-9
references: 12519929
references: J Biol Chem. 2012 Feb 17;287(8):5954-68
references: 22194611
references: Nat Rev Immunol. 2009 Oct;9(10):729-40
references: 19730437
references: Am J Pathol. 2003 Feb;162(2):449-55
references: 12547703
references: Front Immunol. 2012 May 07;3:101
references: 22783250
references: J Immunol. 2005 Jun 15;174(12):8003-10
references: 15944307
references: Neuroscience. 1999;88(4):1073-82
references: 10336122
references: J Innate Immun. 2014;6(2):205-18
references: 23969854
references: J Biol Chem. 1990 Feb 5;265(4):2038-41
references: 2404977
references: J Infect Dis. 2009 Dec 15;200(12):1907-15
references: 19919305
references: Annu Rev Immunol. 2010;28:131-55
references: 19947883
references: J Immunol. 2013 Apr 15;190(8):3831-8
references: 23564577
references: J Immunol. 2005 Sep 15;175(6):3698-706
references: 16148115
references: Perit Dial Int. 2001 Sep-Oct;21(5):501-8
references: 11757835
references: Curr Top Microbiol Immunol. 2006;306:1-25
references: 16909916
references: Immunology. 1982 Jun;46(2):429-41
references: 6919505
references: J Immunol. 2009 Apr 1;182(7):4368-77
references: 19299737
references: Immunology. 1992 Dec;77(4):621-3
references: 1337336
references: Antimicrob Agents Chemother. 2010 Feb;54(2):811-6
references: 19933796
references: Lancet. 2002 Oct 12;360(9340):1144-9
references: 12387964
references: Crit Care. 2014 Mar 24;18(2):R47
references: 24661739
references: FEBS J. 2006 Jun;273(11):2399-406
references: 16704414
references: Mol Med. 2011 Mar-Apr;17(3-4):317-29
references: 21046060
references: Mol Immunol. 2004 Jan;40(10):709-16
references: 14644096
references: J Immunol. 2004 Sep 1;173(5):2909-12
references: 15322146
references: J Immunol. 2008 Jun 1;180(11):7613-21
references: 18490764
references: J Immunol. 2004 Jan 15;172(2):1146-56
references: 14707090
references: J Innate Immun. 2011;3(6):614-22
references: 21677421
references: Adv Exp Med Biol. 2007;598:141-58
references: 17892210
references: Mol Immunol. 2009 Feb;46(5):755-60
references: 18954909
references: Front Immunol. 2013 Jan 09;3:387
references: 23316190
references: Proc Natl Acad Sci U S A. 2004 Nov 30;101(48):16879-84
references: 15550543
references: Mol Immunol. 2011 Aug;48(14):1643-55
references: 21624663
references: Clin Exp Immunol. 2000 Jul;121(1):69-76
references: 10886241
references: Trends Microbiol. 2000 Sep;8(9):402-10
references: 10989307
references: Proc Natl Acad Sci U S A. 2014 Apr 8;111(14):5301-6
references: 24706855
references: J Immunol. 2004 Apr 15;172(8):4987-94
references: 15067080
references: Biochim Biophys Acta. 2007 Feb;1768(2):346-53
references: 17169328
references: Microb Cell Fact. 2011 Dec 02;10:101
references: 22136342
references: Ann Allergy Asthma Immunol. 2004 Dec;93(6):513-22; quiz 523-5, 605
references: 15609759
references: FASEB J. 2004 Sep;18(12):1447-9
references: 15247144
references: Lancet. 1980 May 3;1(8175):947-9
references: 6103300
references: Brain Res Brain Res Rev. 1998 Aug;27(3):243-56
references: 9729408
references: Eur Heart J. 1994 Mar;15(3):418-23
references: 8013522
references: Invest Ophthalmol Vis Sci. 2007 Oct;48(10):4498-508
references: 17898271
references: J Clin Invest. 1982 Oct;70(4):906-13
references: 6288774
references: J Exp Med. 2006 Oct 2;203(10):2271-9
references: 16982811
references: J Immunol. 1998 Mar 15;160(6):2619-25
references: 9510159
references: Blood. 1992 Mar 15;79(6):1532-7
references: 1547345
references: Invest Ophthalmol Vis Sci. 2006 Sep;47(9):4091-7
references: 16936129
references: J Clin Invest. 2002 Jul;110(1):101-8
references: 12093893
references: Scand J Immunol. 1988 May;27(5):489-93
references: 3287594
references: J Immunol. 2012 Jul 1;189(1):304-11
references: 22634613
references: Blood. 2009 Jul 30;114(5):1005-15
references: 19491392
references: J Transl Med. 2009 Apr 23;7:28
references: 19389235
references: J Immunol. 1999 Apr 1;162(7):4336-41
references: 10201966
references: Scand J Immunol. 2009 Jun;69(6):471-8
references: 19439007
references: J Immunol. 2006 Feb 15;176(4):2455-64
references: 16456005
references: Acta Histochem. 1973;45(1):126-32
references: 4197859
references: Ann N Y Acad Sci. 2003 May;992:56-71
references: 12794047
references: J Immunol. 2005 Apr 15;174(8):4901-7
references: 15814717
references: Blood. 2013 Nov 14;122(20):3473-81
references: 23878142
references: Br J Biomed Sci. 1997 Mar;54(1):38-46
references: 9167306
references: J Leukoc Biol. 1987 Apr;41(4):295-301
references: 3471827
references: Curr Issues Mol Biol. 2006 Jan;8(1):11-26
references: 16450883
references: J Immunol. 1999 Dec 15;163(12):6718-24
references: 10586069
references: Trends Immunol. 2010 Apr;31(4):154-63
references: 20153254
references: Eur J Immunol. 1986 Oct;16(10 ):1231-5
references: 2945728
references: J Clin Invest. 1991 Aug;88(2):379-84
references: 1864952
references: Infect Immun. 2005 Aug;73(8):5241-4
references: 16041048
references: Biochim Biophys Acta. 1994 Jun 29;1197(2):109-31
references: 8031824
references: J Immunol. 2003 Jun 1;170(11):5583-9
references: 12759437
references: Am J Pathol. 1994 Jun;144(6):1357-68
references: 7515561
references: J Biochem. 1975 Jan 1;77(1?):55-68
references: 1169237
references: Clin Exp Immunol. 1998 Mar;111(3):477-83
references: 9528886
references: Infect Immun. 2005 Jan;73(1):583-91
references: 15618198
references: J Immunol. 2011 May 1;186(9):5497-505
references: 21441450
references: Biochem J. 1986 Nov 1;239(3):711-6
references: 3827822
references: J Biol Chem. 2005 Oct 14;280(41):34832-9
references: 16091369
references: Biosci Biotechnol Biochem. 2013;77(1):103-10
references: 23291752
references: Mol Immunol. 2001 Aug;38(2-3):221-9
references: 11532283
references: Science. 1996 Jan 19;271(5247):348-50
references: 8553069
references: Mol Immunol. 2003 Jan;39(11):669-75
references: 12493642
references: Front Immunol. 2013 Apr 23;4:93
references: 23630525
references: Proc Natl Acad Sci U S A. 2008 Jul 1;105(26):9023-8
references: 18579773
references: Clin Exp Immunol. 1997 Jan;107(1):1-7
references: 9010248
references: J Immunol. 1995 Apr 15;154(8):4157-65
references: 7535822
references: Eur J Immunol. 1992 Jun;22(6):1447-54
references: 1601035
references: Cell Biol Int. 2002;26(1):55-62
references: 11779221
references: Am Rev Respir Dis. 1988 Aug;138(2):368-75
references: 3264125
references: Eur J Immunol. 2010 Mar;40(3):710-21
references: 20017191
references: EMBO J. 2006 Nov 29;25(23):5569-78
references: 17093496
references: Nat Immunol. 2010 Oct;11(10):928-35
references: 20802484
references: Toxicol Pathol. 2012;40(2):174-82
references: 22109714
references: Clin Dev Immunol. 2012;2012:962927
references: 23320021
references: J Autoimmun. 2009 Nov-Dec;33(3-4):222-30
references: 19819674
references: Semin Immunopathol. 2012 Jan;34(1):151-65
references: 21811895
references: Eur J Immunol. 1989 Jun;19(6):1103-9
references: 2502420
references: Circulation. 2002 Jun 25;105(25):3025-31
references: 12081998
references: J Exp Med. 2000 Oct 2;192(7):1069-74
references: 11015447
references: J Biol Chem. 2007 Jan 26;282(4):2520-8
references: 17132627
references: Scand J Immunol. 1990 Nov;32(5):555-60
references: 2270435
references: J Innate Immun. 2012;4(3):260-72
references: 22116497
references: Proc Natl Acad Sci U S A. 2002 Feb 19;99(4):2152-7
references: 11854512
references: Clin Exp Immunol. 2004 Jul;137(1):117-22
references: 15196251
references: Thromb Haemost. 2014 Jun;111(6):1102-11
references: 24500020
references: PLoS One. 2010 Jan 13;5(1):e8668
references: 20084270
references: Am J Physiol Lung Cell Mol Physiol. 2000 Nov;279(5):L799-805
references: 11053013
references: J Immunol. 2010 Aug 1;185(3):1442-9
references: 20610648
references: J Biol Chem. 1992 Nov 15;267(32):23216-25
references: 1429669
references: Shock. 2004 May;21(5):401-9
references: 15087815
references: J Cell Biol. 1992 Aug;118(4):929-36
references: 1500431
references: Atherosclerosis. 2014 May;234(1):237-43
references: 24685815
references: Ann Rheum Dis. 2003 Nov;62 Suppl 2:ii17-21
references: 14532141
references: Lab Invest. 2011 Jan;91(1):4-11
references: 20921948
references: Infect Immun. 1994 Nov;62(11):5040-7
references: 7927786
references: Nat Rev Immunol. 2014 Dec;14 (12 ):811-20
references: 25394942
references: Perit Dial Int. 2005 Jul-Aug;25(4):394-404
references: 16022098
references: Nat Rev Immunol. 2014 Jun;14(6):392-404
references: 24854589
references: Gastroenterology. 1997 Nov;113(5):1779-84
references: 9352884
references: PLoS One. 2012;7(10):e47095
references: 23091606
references: Am J Med. 1989 Jan;86(1):20-6
references: 2783358
references: Nature. 2001 Nov 22;414(6862):454-7
references: 11719807
references: J Exp Med. 1980 Mar 1;151(3):501-16
references: 6444659
references: Thromb Res. 1995 Oct 15;80(2):179-84
references: 8588195
references: Mol Immunol. 1987 Oct;24(10):1105-11
references: 3316990
references: J Biol Chem. 2010 Mar 5;285(10):7028-34
references: 20068036
references: J Mol Med (Berl). 2010 Feb;88(2):115-20
references: 20062962
references: Perit Dial Int. 2007 Nov-Dec;27(6):654-62
references: 17984427