The many roles of NOX2 NADPH oxidase-derived ROS in immunity.
Reactive oxygen species (ROS) have long been studied in the context of their direct toxic effects on cells. As a result, ROS have conventionally been thought of as a necessary nuisance to aerobic living. However, in recent years, much work has been done to examine the contribution of ROS to the field of immunity. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases were identified as one of the key sources of ROS in immune cells. The NOX2 NADPH oxidase in particular has been assigned multiple roles, functioning as a source of antimicrobial ROS, an activator of many signaling pathways, a participant in chemotaxis, an immune modulator, and a critical player in the initiation of antigen cross-presentation. Furthermore, recent studies have revealed a novel role for the NOX2 NADPH oxidase in the activation of autophagy, a cellular degradative pathway. Here, we examine these functions of NOX2 NADPH oxidase in immunity.
Lam
Grace Y
GY
Cell Biology Program, Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada, M5G 1X8.
Huang
Ju
J
Brumell
John H
JH
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D001343:Autophagy / Q000276:immunology; D002633:Chemotaxis / Q000276:immunology; D004789:Enzyme Activation / Q000276:immunology; D006801:Humans; D008562:Membrane Glycoproteins / Q000276:immunology*; D009249:NADP / Q000276:immunology*; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000276:immunology*; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology
D008562:Membrane Glycoproteins; D017382:Reactive Oxygen Species; D009249:NADP; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases
J Biol Chem. 2006 Jul 14;281(28):19179-87
16702227
Am J Respir Crit Care Med. 2003 Feb 1;167(3):431-7
12554628
Eur J Immunol. 2010 May;40(5):1461-72
20162553
J Clin Invest. 2007 Oct;117(10):3020-8
17909630
J Exp Med. 1988 Apr 1;167(4):1459-71
2833557
Nature. 2002 Mar 21;416(6878):291-7
11907569
Cell Host Microbe. 2009 Jun 18;5(6):527-49
19527881
Hypertension. 2003 Apr;41(4):925-31
12629036
World J Gastroenterol. 2010 Mar 14;16(10):1258-66
20222171
Oncogene. 2006 Oct 30;25(51):6731-48
17072325
Autophagy. 2007 Jul-Aug;3(4):371-3
17438362
FEBS Lett. 2004 Feb 27;560(1-3):7-13
15017976
Cell Death Differ. 2009 Jul;16(7):976-83
19444282
Autophagy. 2008 Jan;4(1):73-5
17932464
Biochem Pharmacol. 2009 Apr 15;77(8):1303-15
19071092
Cell Metab. 2008 Nov;8(5):425-36
19046573
Biochem Biophys Res Commun. 2008 Jul 11;371(4):834-40
18468509
Science. 2005 Mar 11;307(5715):1630-4
15761154
Proc Natl Acad Sci U S A. 2001 Mar 13;98(6):3001-5
11248021
Infect Immun. 2009 Jun;77(6):2385-91
19307214
Microbes Infect. 2009 May-Jun;11(6-7):671-9
19379824
J Leukoc Biol. 2005 May;77(5):598-625
15689384
J Biol Chem. 2001 Jun 22;276(25):23077-83
11304537
Proc Natl Acad Sci U S A. 2006 Sep 26;103(39):14578-83
16983090
Nat Genet. 2003 Jan;33(1):25-32
12461526
Genes Immun. 2008 Sep;9(6):561-5
18580884
J Biol Chem. 2001 Mar 16;276(11):8261-8
11102453
Cell Microbiol. 2006 Apr;8(4):668-76
16548892
Rejuvenation Res. 2005 Spring;8(1):3-5
15798367
J Immunol. 2003 May 15;170(10):5302-8
12734380
Cell Microbiol. 2006 Dec;8(12):1922-31
16848789
J Biol Chem. 2009 Jan 16;284(3):1694-701
19028680
Int J Hematol. 2006 Oct;84(3):193-8
17050190
J Clin Immunol. 2009 Jan;29(1):46-56
18690522
Blood. 2008 Nov 1;112(9):3867-77
18711001
Medicine (Baltimore). 2000 May;79(3):155-69
10844935
Infect Immun. 2009 Jun;77(6):2517-29
19349423
Blood. 2008 Dec 1;112(12):4712-22
18682599
Nat Rev Microbiol. 2009 May;7(5):355-66
19369951
Infect Immun. 1986 Aug;53(2):252-6
3015798
Circ Res. 2003 Aug 22;93(4):311-20
12881478
J Immunol. 2001 Jan 15;166(2):1206-13
11145703
Infect Immun. 1992 Apr;60(4):1263-7
1312514
J Immunol. 2004 Nov 1;173(9):5730-8
15494525
J Leukoc Biol. 2006 Dec;80(6):1224-30
16908516
Biochem J. 1993 Feb 15;290 ( Pt 1):173-8
8439286
Antioxid Redox Signal. 2006 Jan-Feb;8(1-2):152-62
16487049
Clin Exp Immunol. 2001 Jul;125(1):48-55
11472425
Cell. 2007 Jan 26;128(2):325-39
17254970
Microbes Infect. 2007 Aug;9(10):1176-87
17720603
J Clin Invest. 1998 Dec 15;102(12):2146-55
9854050
J Immunol. 2004 Jan 1;172(1):636-43
14688376
J Biol Chem. 1994 Dec 30;269(52):33028-34
7806531
Cell Microbiol. 2001 Dec;3(12):811-23
11736993
Microbiology (Reading). 2009 Apr;155(Pt 4):1004-1015
19332803
J Immunol. 2000 Nov 1;165(9):5238-44
11046057
Int J Hematol. 2001 Aug;74(2):125-33
11594511
FASEB J. 2007 Mar;21(3):927-34
17194695
Science. 2000 Mar 3;287(5458):1655-8
10698741
Nature. 2008 Oct 30;455(7217):1244-7
18815593
Infect Immun. 1994 Oct;62(10):4445-53
7927708
J Immunol. 2009 Dec 1;183(11):7497-504
19917703
Cell Microbiol. 2007 Apr;9(4):891-909
17087732
Nature. 2008 Oct 30;455(7217):1186-7
18972010
Eur J Immunol. 1998 Nov;28(11):3886-90
9842932
Cell. 2007 Jul 13;130(1):165-78
17632063
Physiol Rev. 2007 Jan;87(1):245-313
17237347
Biochemistry. 2002 Jun 18;41(24):7743-50
12056906
J Biol Chem. 2006 Apr 21;281(16):11374-83
16495224
Autophagy. 2007 Sep-Oct;3(5):442-51
17568179
Circ Res. 2010 May 14;106(9):1489-97
20360249
Proc Natl Acad Sci U S A. 2009 Apr 14;106(15):6226-31
19339495
Nature. 2008 Feb 28;451(7182):1069-75
18305538
Hepatology. 2008 Oct;48(4):1292-301
18785192
Infect Immun. 1998 Sep;66(9):4474-83
9712803
Autophagy. 2007 Mar-Apr;3(2):117-25
17204850
Free Radic Biol Med. 2008 Apr 15;44(8):1529-35
18275858
Eur Cytokine Netw. 2002 Apr-Jun;13(2):242-9
12101081
Clin Rev Allergy Immunol. 2010 Feb;38(1):3-10
19504359
J Infect Dis. 2003 May 15;187(10):1609-15
12721941
J Leukoc Biol. 2006 Feb;79(2):330-8
16275888
Clin Exp Immunol. 2000 May;120(2):351-5
10792387
Nat Cell Biol. 2001 Jul;3(7):675-8
11433300
Science. 2004 Mar 5;303(5663):1532-5
15001782
Nature. 2004 Feb 26;427(6977):853-8
14985765
Exp Mol Med. 2009 Mar 31;41(3):171-9
19293636
Cell. 2004 Dec 17;119(6):753-66
15607973
Chem Res Toxicol. 1997 Oct;10(10):1080-9
9348429
Biochem J. 2009 May 1;419(3):603-10
18983267
Biochem Pharmacol. 1995 Apr 18;49(8):1079-84
7748188
Biochem Biophys Res Commun. 1981 Apr 15;99(3):781-8
6894695
Antioxid Redox Signal. 2009 Oct;11(10):2409-27
19388824
Annu Rev Immunol. 2005;23:197-223
15771570
J Clin Periodontol. 1986 Apr;13(4):330-1
3458728
Infect Immun. 2010 Jan;78(1):80-7
19858301
Biochim Biophys Acta. 1988 Sep 16;971(2):189-96
2844287
Cell Death Differ. 2009 Jul;16(7):1040-52
19407826
J Biol Chem. 2002 Nov 1;277(44):42136-43
12207012
Cell Immunol. 2010;263(2):166-71
20392440
Infect Immun. 1988 May;56(5):1162-6
3258584
J Biol Chem. 1992 Dec 25;267(36):25709-13
1464587
EMBO J. 2007 Feb 21;26(4):1176-86
17290225
J Immunol. 1999 Dec 15;163(12):6732-40
10586071
Biochem J. 2009 Jan 1;417(1):1-13
19061483
Blood. 2005 Dec 1;106(12):3962-9
16099876
Nature. 2003 Sep 25;425(6956):397-402
14508489
Parasitol Res. 2007 Jun;101(1):85-9
17252269
J Immunol. 1986 Jun 15;136(12):4617-22
3011897
Biochem J. 2000 Apr 1;347 Pt 1:285-9
10727429
J Immunol. 2005 Nov 1;175(9):5596-600
16237045
Antioxid Redox Signal. 2008 Sep;10(9):1549-64
18479206
Proc Natl Acad Sci U S A. 2001 Feb 27;98(5):2561-5
11226278
Proc Natl Acad Sci U S A. 2010 Feb 23;107(8):3546-51
20142487
Immunol Cell Biol. 2010 Feb;88(2):197-204
19935767
Sci Signal. 2009 Sep 15;2(88):ra54
19755710
Nature. 2009 Aug 27;460(7259):1159-63
19641494
EMBO J. 2008 Apr 9;27(7):1110-21
18337753
Mol Aspects Med. 2006 Oct-Dec;27(5-6):444-54
16978688
Nat Cell Biol. 2001 Jul;3(7):679-82
11433301
Free Radic Biol Med. 2002 Sep 15;33(6):774-97
12208366
Semin Immunopathol. 2008 Jul;30(3):237-53
18574584
Free Radic Biol Med. 2005 May 1;38(9):1188-96
15808416
Antioxid Redox Signal. 2010 Aug 15;13(4):525-37
19958170
Immunol Rev. 2007 Oct;219:103-17
17850485
Mol Med Today. 1996 Mar;2(3):129-35
8796870
Virology. 2006 Jun 5;349(2):254-63
16643977
Biochemistry. 1994 Mar 15;33(10):2907-11
8130204
EMBO J. 2007 Apr 4;26(7):1749-60
17347651
Proc Natl Acad Sci U S A. 2009 Feb 17;106(7):2313-8
19139406
J Leukoc Biol. 2004 Oct;76(4):760-81
15240752
Nat Immunol. 2001 Mar;2(3):211-5
11224519
J Clin Invest. 2003 Dec;112(11):1732-40
14660749
Trends Cell Biol. 2007 Sep;17(9):422-7
17804237
J Infect Dis. 2010 Jan 1;201(1):97-105
19919301
J Biol Chem. 1995 Oct 27;270(43):25557-63
7592726
Microbes Infect. 2001 Nov-Dec;3(14-15):1313-20
11755420
J Exp Med. 1997 Jan 20;185(2):207-18
9016870
J Biol Chem. 2002 Mar 22;277(12):10121-8
11796733
J Med Microbiol. 2003 Aug;52(Pt 8):643-651
12867557
J Biol Chem. 2002 Sep 6;277(36):32546-51
12093794
Free Radic Biol Med. 1998 Jan 15;24(2):318-25
9433907
Cell. 2006 Jul 14;126(1):205-18
16839887
J Med Invest. 2009 Feb;56(1-2):33-41
19262012
Autophagy. 2008 Jul;4(5):607-11
18552553
Infect Immun. 2009 Apr;77(4):1324-36
19204089
Free Radic Biol Med. 2005 Mar 1;38(5):616-30
15683718
Sci STKE. 2000 Oct 10;2000(53):pe1
11752613
Nat Rev Cancer. 2005 Nov;5(11):886-97
16239905
J Cell Biol. 2007 Jan 15;176(2):231-41
17210947
Nat Immunol. 2010 Jan;11(1):55-62
19898471
Cell Signal. 1996 Jun;8(4):291-6
8842530
Science. 2004 Nov 5;306(5698):1037-40
15528445
Biochem Pharmacol. 2006 Feb 28;71(5):551-64
16337153
Nat Rev Immunol. 2004 Mar;4(3):181-9
15039755
Biochem Biophys Res Commun. 2004 Apr 9;316(3):720-30
15033459
Eur J Biochem. 1997 Jan 15;243(1-2):240-6
9030745
Microbiol Immunol. 2007;51(12):1161-70
18094534
Mol Pharmacol. 1998 Mar;53(3):497-503
9495817
Cell. 2002 Nov 27;111(5):607-10
12464172
Nat Rev Immunol. 2007 Oct;7(10):767-77
17767194
Am J Hypertens. 2008 Apr;21(4):477-81
18246055
Bull N Y Acad Med. 1989 Jan;65(1):69-79
2557949
J Immunol. 1992 Nov 1;149(9):3008-15
1383336
J Biol Chem. 2008 Jun 20;283(25):16961-5
18420576
Immunol Rev. 2009 Jan;227(1):203-20
19120486
J Biol Chem. 1992 May 25;267(15):10215-8
1316893
Histochem Cell Biol. 2004 Oct;122(4):277-91
15293055
J Infect Dis. 2000 Jun;181(6):1885-90
10837166
J Biol Chem. 2008 Jan 25;283(4):2108-19
18029359
J Hypertens. 2004 Jun;22(6):1151-6
15167450
Biochemistry. 2003 Apr 22;42(15):4520-6
12693948
Curr Biol. 2001 Oct 16;11(20):1631-5
11676926
Plant Physiol. 2007 Jan;143(1):291-9
17098847
EMBO J. 2009 Oct 7;28(19):3015-26
19713938
Cell Death Differ. 2008 Jan;15(1):171-82
17917680
Cell. 2006 Jul 14;126(1):107-20
16839880
Immunol Rev. 2005 Oct;207:145-57
16181333
Antioxid Redox Signal. 2009 Jun;11(6):1313-33
19072143
Exp Mol Med. 2003 Oct 31;35(5):325-35
14646585
Proc Natl Acad Sci U S A. 2004 Sep 21;101(38):13867-72
15353593
Eur J Immunol. 2006 Jun;36(6):1364-73
16703568
Free Radic Biol Med. 1999 Jan;26(1-2):232-8
9890657
Semin Immunol. 2009 Aug;21(4):233-41
19502083
Infect Immun. 1987 Jul;55(7):1641-6
3110067
Autophagy. 2008 Jan;4(1):110-2
18059159
J Leukoc Biol. 2004 Dec;76(6):1180-6
15371490
J Immunol. 2010 May 1;184(9):5141-50
20348422
J Biol Chem. 2006 Oct 13;281(41):30373-82
16857678
Autophagy. 2006 Jul-Sep;2(3):156-8
16874057