Innate immunity, coagulation and placenta-related adverse pregnancy outcomes.
Maternal immunity undergoes subtle adjustment in order to tolerate the semi-allogeneic embryo and maintain the host defense against potential pathogens. Concomitantly, coagulation systems change from an anti-coagulant state to a pro-coagulant state to meet the hemostatic challenge of placentation and delivery. Innate immunity and blood coagulation systems are the first line of defense to protect a host against exogenous challenges, including alloantigens and mechanical insults, and preserve the integrity of an organism. The interactions between coagulation and immune systems have been extensively studied. Immune cells play a pivotal role in the initiation of the coagulation cascade, whereas coagulation proteases display substantial immuno-modulatory effects. Upon exogenous challenges, the immune and coagulation systems are capable of potentiating each other leading to a vicious cycle. Natural killer (NK) cells, macrophages (Mphis) and dendritic cells (DCs) are three major innate immune cells that have been demonstrated to play essential roles in early pregnancy. However, immune maladaptation and hemostatic imbalance have been suggested to be responsible for adverse pregnant outcomes, such as preeclampsia (PE), miscarriage, recurrent spontaneous abortion (RSA) and intrauterine growth restriction (IUGR). In this review, we will summarize the mutual regulation between blood coagulation and innate immune systems as well as their roles in the maintenance of normal pregnancy and in the pathogenesis of adverse pregnancy outcomes.
Li
Min
M
Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut 06520-8063, USA.
Huang
S Joseph
SJ
D000026:Abortion, Habitual / Q000276:immunology; D000022:Abortion, Spontaneous / Q000276:immunology; D001777:Blood Coagulation; D003713:Dendritic Cells / Q000166:cytology; D005260:Female; D005317:Fetal Growth Retardation / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D007694:Killer Cells, Natural / Q000166:cytology; D008264:Macrophages / Q000166:cytology; D010920:Placenta / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000276:immunology; D011247:Pregnancy; D011250:Pregnancy Complications, Hematologic; D011256:Pregnancy Outcome
J Reprod Immunol. 2003 Feb;58(1):27-47
12609523
Am J Reprod Immunol. 2002 May;47(5):283-8
12148543
J Clin Invest. 2008 Dec;118(12):3954-65
19033665
J Soc Gynecol Investig. 2004 Sep;11(6):342-52
15350246
Blood. 2004 Dec 15;104(13):3878-85
15339848
Placenta. 2000 Sep;21(7):693-702
10985973
Science. 1983 May 13;220(4598):728-31
6836310
N Engl J Med. 2002 Jul 4;347(1):19-25
12097536
Obstet Gynecol. 1992 Jan;79(1):19-26
1727579
Int Immunol. 1993 Feb;5(2):233-8
8095800
Placenta. 1991 Mar-Apr;12(2):173-82
1678517
Crit Care Med. 2005 Feb;33(2):368-72
15699841
Ann N Y Acad Sci. 2008 Apr;1127:67-72
18443332
J Leukoc Biol. 1998 Jan;63(1):40-50
9469471
J Clin Invest. 1997 May 15;99(10):2446-51
9153288
J Biol Chem. 2001 Apr 6;276(14):11199-203
11278252
J Biol Chem. 2000 Jul 7;275(27):20374-81
10877842
Obstet Gynecol Surv. 2000 Oct;55(10):650-60
11023206
Biochemistry. 1984 Jan 31;23(3):397-400
6704377
Am J Obstet Gynecol. 2009 Feb;200(2):151.e1-9; discussion e1-5
19070828
Biochem Biophys Res Commun. 1989 Sep 29;163(3):1404-11
2675842
J Endocrinol. 1998 Dec;159(3):459-67
9834463
Am J Perinatol. 2001 Jun;18(4):195-201
11444363
Blood. 2001 May 15;97(10):3109-16
11342437
Immunol Rev. 2000 Oct;177:204-16
11138777
Crit Care Med. 2000 Sep;28(9 Suppl):S77-80
11007204
Blood. 2000 Jul 1;96(1):170-5
10891447
Br J Haematol. 1992 Oct;82(2):295-301
1419810
Development. 1996 Jul;122(7):2271-81
8681807
Proc Natl Acad Sci U S A. 1988 Oct;85(20):7462-6
2971972
Nat Rev Immunol. 2002 Sep;2(9):656-63
12209134
Aust N Z J Obstet Gynaecol. 1999 Nov;39(4):484-7
10687770
Hum Reprod. 2007 Oct;22(10):2733-42
17704101
Nature. 2008 Apr 3;452(7187):654-8
18305483
Hematol Oncol Clin North Am. 2000 Oct;14(5):1117-31
11005037
Arterioscler Thromb Vasc Biol. 2007 Jun;27(6):1463-70
17379836
Biol Chem. 1998 Aug-Sep;379(8-9):973-86
9792430
Circ Res. 1995 Sep;77(3):503-9
7641321
Mol Endocrinol. 2006 Nov;20(11):2724-33
16772530
Eur J Obstet Gynecol Reprod Biol. 2002 Feb 10;101(1):6-14
11803092
Obstet Gynecol. 2008 Aug;112(2 Pt 1):320-4
18669729
J Reprod Immunol. 2005 Apr;65(2):101-10
15811515
Trends Immunol. 2004 Oct;25(10):536-42
15364056
Proc Natl Acad Sci U S A. 2000 May 9;97(10):5255-60
10805786
Semin Thromb Hemost. 1996;22(2):145-50
8807711
Biomaterials. 2008 Jul;29(21):3084-90
18452987
J Cell Physiol. 1986 Sep;128(3):485-90
3745283
J Biol Chem. 1994 Oct 21;269(42):26486-91
7929370
Thromb Haemost. 2000 Dec;84(6):1087-94
11154118
Placenta. 1983 Oct-Dec;4(4):397-413
6634666
J Immunol. 2002 Sep 1;169(5):2602-10
12193731
Biol Reprod. 2003 Jul;69(1):1-7
12620937
J Reprod Immunol. 1989 Sep;16(1):1-17
2689644
Int Arch Allergy Appl Immunol. 1972;43(6):879-86
4267205
Biol Reprod. 2003 May;68(5):1496-504
12606489
Fertil Steril. 2003 Sep;80(3):590-4
12969703
BMJ. 1999 Jul 24;319(7204):245-9
10417093
Nat Rev Immunol. 2006 Aug;6(8):584-94
16868549
Semin Immunol. 2001 Aug;13(4):235-41
11437631
Nat Rev Genet. 2006 Mar;7(3):185-99
16485018
J Pathol. 2008 Feb;214(3):328-36
18069648
Blood. 2002 May 15;99(10):3676-82
11986223
J Leukoc Biol. 1994 Mar;55(3):410-22
7509844
N Engl J Med. 1999 Jan 7;340(1):9-13
9878639
Mol Cell Biol. 1988 Dec;8(12):5588-92
2854203
Transfus Med. 2001 Dec;11(6):403-17
11851938
Am J Pathol. 2006 Feb;168(2):445-52
16436659
Hum Reprod. 2009 Jan;24(1):185-97
18854409
Endocr Rev. 2005 Dec;26(7):877-97
15901666
Arterioscler Thromb Vasc Biol. 2008 Aug;28(8):1491-8
18497306
J Exp Med. 2002 Sep 2;196(5):565-77
12208873
Lancet. 2000 Apr 15;355(9212):1292-3
10776739
J Exp Med. 2004 Oct 18;200(8):957-65
15477349
Immunology. 1990 Aug;70(4):446-52
1697563
Blood. 2006 Apr 15;107(8):3173-80
16380449
Am J Physiol Regul Integr Comp Physiol. 2006 Jan;290(1):R1-R10
16352854
J Immunol. 1996 Apr 1;156(7):2406-12
8786298
Immunol Res. 1996;15(2):141-50
8839782
Nat Immunol. 2006 Mar;7(3):241-6
16482172
J Exp Med. 2006 Sep 4;203(9):2165-75
16923853
Curr Opin Immunol. 2001 Feb;13(1):114-9
11154927
Am J Reprod Immunol. 2008 May;59(5):371-87
18405308
J Reprod Immunol. 2006 Dec;72(1-2):60-73
16806486
N Engl J Med. 1999 Aug 19;341(8):586-92
10451465
Placenta. 1994 Dec;15(8):819-35
7886023
Trends Immunol. 2001 Nov;22(11):633-40
11698225
Tissue Antigens. 2004 Jan;63(1):1-12
14651517
J Immunol. 1995 Jul 15;155(2):895-901
7608566
Early Hum Dev. 2000 Aug;59(2):77-84
10996745
J Immunol. 1994 Oct 15;153(8):3664-72
7523500
Br J Obstet Gynaecol. 1992 Jul;99(7):547-53
1525093
Lab Invest. 2001 Aug;81(8):1143-52
11502865
J Immunol. 1999 May 1;162(9):5466-76
10228026
Lancet. 2003 Mar 15;361(9361):901-8
12648968
Crit Care Med. 2001 Jan;29(1):134-9
11176173
Blood. 2002 Jun 1;99(11):4015-20
12010802
J Soc Gynecol Investig. 2004 Jan;11(1):42-4
14706682
J Exp Med. 1994 Apr 1;179(4):1253-9
8145042
Immunology. 1996 May;88(1):76-81
8707354
Blood. 1995 Aug 1;86(3):1027-34
7620156
J Reprod Fertil. 1993 Nov;99(2):609-15
8107046
Chem Immunol Allergy. 2005;88:163-180
16129945
Med Electron Microsc. 2003 Dec;36(4):253-62
16228658
BMJ. 1990 Nov 17;301(6761):1111
2252919
J Clin Invest. 2002 Jan;109(1):41-50
11781349
J Biol Chem. 2004 Apr 2;279(14):13729-37
14736878
Placenta. 1999 Mar-Apr;20(2-3):229-33
10195746
Thromb Res. 2004;114(5-6):409-14
15507271
J Biol Chem. 2001 Sep 7;276(36):33947-51
11431478
Placenta. 2003 Apr;24 Suppl A:S16-20
12842409
Trends Immunol. 2004 Sep;25(9):489-95
15324742
J Immunol. 1995 May 1;154(9):4768-77
7536780
Blood. 1999 Nov 15;94(10):3413-20
10552951
J Exp Med. 2004 Oct 18;200(8):951-5
15492121
Am J Physiol. 1999 Jun;276(6):C1391-7
10362602
Proc Natl Acad Sci U S A. 1990 Sep;87(18):6934-8
2169613
J Leukoc Biol. 2006 Sep;80(3):572-80
16816146
J Surg Res. 1991 May;50(5):436-41
2038182
Thromb Res. 2008;122(3):359-65
18295304
Crit Care Med. 2002 May;30(5 Suppl):S288-93
12004250
J Pathol Bacteriol. 1967 Apr;93(2):569-79
6054057
Am J Physiol. 1999 Oct;277(4):G801-9
10516146
J Clin Endocrinol Metab. 2004 Feb;89(2):812-22
14764800
J Immunol. 2003 Jul 15;171(2):669-77
12847232
J Exp Med. 1996 Mar 1;183(3):821-7
8642286
J Clin Invest. 2000 Mar;105(5):577-87
10712429
Nat Med. 2006 Sep;12(9):1065-74
16892062
Proc Natl Acad Sci U S A. 1994 Sep 13;91(19):8767-71
7522321
Thromb Haemost. 2002 Aug;88(2):267-73
12195699
Am J Hematol. 1994 Jul;46(3):241-4
8192155
Cytotherapy. 2008;10(7):720-9
18985478
Immunol Today. 1998 Dec;19(12):568-74
9864948
Biol Reprod. 2003 Oct;69(4):1438-46
12826583
Br Med Bull. 1997 Jan;53(1):96-108
9158287
Thromb Haemost. 1994 Oct;72(4):627-33
7878643
Lancet. 2005 Feb 26-Mar 4;365(9461):785-99
15733721
Arthritis Rheum. 2000 Sep;43(9):2064-72
11014358
Immunol Cell Biol. 1999 Oct;77(5):404-10
10540206
BMJ. 1989 Aug 26;299(6698):541-5
2507063
Pediatrics. 1993 Apr;91(4):807-11
7681941
J Immunol Methods. 1990 Sep 14;132(2):181-9
2145368
Clin Exp Immunol. 1999 Sep;117(3):550-5
10469061
N Engl J Med. 1994 Sep 22;331(12):753-9
7520533
J Infect Dis. 1996 Jan;173(1):172-9
8537655