Coagulation and Immune in Thrombosis

doi:10.3969/j.issn.1673-5765.2020.01.008

Abstract

Abstract:

Thrombosis is the result of blood coagulation caused by platelet and coagulation factor activation after vascular injury. Studies have shown that there are extensive links between coagulation and inflammation, involving the interaction among the blood cascade system, immune cells and vascular endothelial cells. Platelets, tissue factors, thrombin, contact activation system and complement system jointly promote thrombosis, and activated proinflammatory responses. Plasminogen activation system not only activates fibrinolysis but also promotes the inflammatory process associated with thrombosis. These pathophysiological reactions ultimately lead to thromboinflammation process. This article introduced the relationship between coagulation and immune and the role of immune in thrombosis, to provide reference for the future research on therapeutic targets for inflammatory and thrombotic diseases.

Key words: Coagulation; Immune; Thrombosis

摘要：

血栓形成是血管损伤后血小板活化、凝血因子激活导致凝血的过程，研究表明凝血和炎症之间存在广泛的联系，涉及血液级联系统、免疫细胞和血管内皮细胞之间的相互作用。血小板、组织因子、凝血酶、接触激活系统、补体系统在促进血栓形成过程启动促炎反应，纤溶酶原激活系统在激活纤溶的同时促进与血栓形成有关的炎症过程，这些综合因素最终导致血栓-炎症的产生。本文就凝血与免疫的关系及其在血栓形成中的作用作简要的阐述，旨在为今后研究炎症和血栓性疾病的治疗靶点提供思路。

关键词: 凝血; 免疫; 血栓

ZHANG Wei, YAN Tao. Coagulation and Immune in Thrombosis[J]. Chinese Journal of Stroke, 2020, 15(01): 51-56.

张薇，阎涛. 血栓形成中的凝血与免疫[J]. 中国卒中杂志, 2020, 15(01): 51-56.

References

[1] NIESWANDT B，KLEINSCHNITZ C，STOLL

G. Ischaemic stroke：a thrombo-inflammatory

disease?[J]. J Physiol，2011，589（17）：4115-4123.

[2] STOLL G，NIESWANDT B. Thrombo-inflammation

in acute ischaemic stroke - implications for

treatment[J]. Nat Rev Neurol，2019，15（8）：473-

481.

[3] EKDAHL K N，TERAMURA Y，HAMAD O A，et

al. Dangerous liaisons：complement，coagulation，

and kallikrein/kinin cross-talk act as a linchpin

in the events leading to thromboinflammation[J].

Immunol Rev，2016，274（1）：245-269.

[4] SAHNI A，SAHNI S K，FRANCIS C W.

Endothelial cell activation by IL-1β in the presence

of fibrinogen requires αVβ3[J]. Arterioscler Thromb

Vasc Biol，2005，25（25）：2222-2227.

[5] MEZGER M，NORDING H，SAUTER R，et

al. Platelets and immune responses during

thromboinflammation[J/OL]. Front Immunol，2019，

10：1731. https：//doi.org/10.3389/fimmu.2019.01731.

[6] CLARK S R，MA A C，TAVENER S A，et al.

Platelet TLR4 activates neutrophil extracellular traps

to ensnare bacteria in septic blood[J]. Nat Med，2007，

13（4）：463-469.

[7] REYES-GARCÍA A M L，AROCA A，ARROYO

AB，et al. Neutrophil extracellular trap components

increase the expression of coagulation factors[J].

Biomed Rep，2019，10（3）：195-201.

[8] SILK E，ZHAO H，WENG H，et al. The role

of extracellular histone in organ injury[J/OL].

Cell Death Dis，2017，8（5）：e2812. https：//doi.

org/10.1038/cddis.2017.52.

[9] MANGOLD A，ALIAS S，SCHERZ T，et al.

Coronary neutrophil extracellular trap burden and

deoxyribonuclease activity in ST-elevation acute

coronary syndrome are predictors of ST-segment

resolution and infarct size[J]. Circ Res，2015，116（7）：

1182-1192.

[10] PEREZ-DE-PUIG I，MIRÓ-MUR F，FRANCESC，FERRER-FERRER M，et al. Neutrophil recruitment

to the brain in mouse and human ischemic stroke[J].

Acta Neuropathol，2015，129（2）：239-257.

[11] MARTINOD K，WAGNER D D. Thrombosis：

tangled up in NETs[J]. Blood，2014，123（18）：2768-

2776.

[12] ZHANG X，MCGEOCH S C，JOHNSTONE A

M，et al. Platelet-derived microparticle count and

surface molecule expression differ between subjects

with and without type 2 diabetes，independently of

obesity status[J]. J Thromb Thrombolysis，2014，37

（4）：455-463.

[13] LAFFONT B，CORDUAN A，ROUSSEAU M，et al.

Platelet microparticles reprogram macrophage gene

expression and function[J]. Thromb Haemost，2017，

115（2）：311-323.

[14] BAJ-KRZYWORZEKA M，MAJKA M，PRATICO

D，et al. Platelet-derived microparticles stimulate

proliferation，survival，adhesion，and chemotaxis of

hematopoietic cells[J]. Exp Hematol，2002，30（5）：

450-459.

[15] OWENS A P 3rd，MACKMAN N. Microparticles

in hemostasis and thrombosis[J]. Circ Res，2011，108

（10）：1284-1297.

[16] CHIVA-BLANCH G，LAAKE K，MYHRE P，et

al. Platelet-，monocyte-derived and tissue factorcarrying

circulating microparticles are related

to acute myocardial infarction severity[J/OL].

PLoS One，2017，12（2）：e0172558. https：//doi.

org/10.1371/journal.pone.0172558.

[17] SCHWERTZ H，TOLLEY N D，FOULKS J M，et al.

Signal-dependent splicing of tissue factor pre-mRNA

modulates the thrombogenecity of human platelets[J].

J Exp Med，2006，203（11）：2433-2440.

[18] CIRILLO P，CALÌ G，GOLINO P，et al. Tissue

factor binding of activated factor VII triggers smooth

muscle cell proliferation via extracellular signalregulated

kinase activation[J]. Circulation，2004，109

（23）：2911-2916.

[19] OWENS A P 3rd，MACKMAN N. Sources of tissue

factor that contribute to thrombosis after rupture of

an atherosclerotic plaque[J]. Thromb Res，2012，129

（Suppl 2）：S30-S33.

[20] LI S，CHEN H，REN J，et al. MicroRNA-223

inhibits tissue factor expression in vascular

endothelial cells[J]. Atherosclerosis，2014，237（2）：

514-520.

[21] DEMETZ G，SEITZ I，STEIN A，et al. Tissue

Factor–Factor VIIa complex induces cytokine

expression in coronary artery smooth muscle cells[J].

Atherosclerosis，2010，212（2）：466-471.

[22] CAMERER E，HUANG W，COUGHLIN S R.

Tissue factor- and factor X-dependent activation of

protease-activated receptor 2 by factor VIIa[J]. Proc

Natl Acad Sci USA，2000，97（10）：5255-5260.

[23] KAHN M L，ZHENG Y W，HUANG W，et

al. A dual thrombin receptor system for platelet

activation[J]. Nature，1998，394（6694）：690-694.

[24] HENN V，SLUPSKY J R，GRÄFE M，et al. CD40

ligand on activated platelets triggers an inflammatory

reaction of endothelial cells[J]. Nature，1998，391

（6667）：591-594.

[25] SOWER L E，FROELICH C J，CARNEY D H，et al.

Thrombin induces IL-6 production in fibroblasts and

epithelial cells. Evidence for the involvement of the

seven-transmembrane domain（STD）receptor for

alpha-thrombin[J]. J Immunol，1995，155（2）：895-

901.

[26] RAHMAN A，FAZAL F. Hug tightly and say

goodbye：role of endothelial ICAM-1 in leukocyte

transmigration[J]. Antioxid Redox Signal，2009，11

（4）：823-839.

[27] VON BRUHL M L，STARK K，STEINHART A，et

al. Monocytes，neutrophils，and platelets cooperate

to initiate and propagate venous thrombosis in mice

in vivo[J]. J Exp Med，2012，209（4）：819-835.

[28] Renné T. The procoagulant and proinflammatory

plasma contact system[J]. Semin Immunopathol，

2011，34（1）：31-41.

[29] RENNÉ T，SCHMAIER A H，NICKEL K F，et al.

In vivo roles of factor Ⅻ[J]. Blood，2012，120（22）：

4296-4303.

[30] AMBALATHINGAL G R，FRANCIS R S，SMYTH

M J，et al. BK Polyomavirus：clinical aspects，

immune regulation，and emerging therapies[J]. Clin

Microbiol Rev，2017，30（2）：503-528.

[31] GÖB E，REYMANN S，LANGHAUSER F，et al.

Blocking of plasma kallikrein ameliorates stroke by

reducing thromboinflammation[J]. Ann Neurol，2015，

77（5）：784-803.

[32] LANGHAUSER F，GÖB E，KRAFT P，et al.

Kininogen deficiency protects from ischemic

neurodegeneration in mice by reducing thrombosis，

blood-brain barrier damage，and inflammation[J].

Blood，2012，120（19）：4082-4092.

[33] SCHRAUFSTATTER I U，TRIEU K，SIKORA

L，et al. Complement c3a and c5a induce different

signal transduction cascades in endothelial cells[J]. J

Immunol，2002，169（4）：2102-2110.

[34] RITIS K，DOUMAS M，MASTELLOS D，et al. A

novel C5aR-tissue factor crosstalk in neutrophils

links innate immunity to coagulation pathways[J].Mol Immunol，2007，44（1）：266.

[35] KRARUP A，GULLA K C，GÁL P，et al. The action

of MBL-associated serine protease 1（MASP1）on

factor ⅩⅢ and fibrinogen[J]. Biochim Biophys Acta，

2008，1784（9）：1294-1300.

[36] KOZARCANIN H，LOOD C，MUNTHE-FOG

L，et al. The lectin complement pathway serine

proteases（MASPs）represent a possible crossroad

between the coagulation and complement systems in

thromboinflammation[J]. J Thromb Haemost，2016，

14（3）：531-545.

[37] CUADRADO E，ORTEGA L，HERNÁNDEZGUILLAMON

M，et al. Tissue plasminogen activator

（t-PA）promotes neutrophil degranulation and MMP-

9 release[J]. J Leukoc Biol，2008，84（1）：207-214.

[38] ABRAHAM E，GYETKO M R，KUHN K，et al.

Urokinase-type plasminogen activator potentiates

lipopolysaccharide-induced neutrophil activation[J].

J Immunol，2003，170（11）：5644-5651.

[39] MEHRA A，ALI C，PARCQ J，et al.

The plasminogen activation system in

neuroinflammation[J]. Biochim Biophys Acta，2015，

1862（3）：395-402.

[40] FOLEY J H，PETERSON E A，LEI V，et al.

Interplay between fibrinolysis and complement：

plasmin cleavage of iC3b modulates immune

responses[J]. J Thromb Haemost，2015，13（4）：610-

618.