Mechanism of tissue factor production by monocytes stimulated with neutrophil elastase

被引：10

作者：

Kawata, Jin ^{[1
]}

Aoki, Manabu ^{[1
]}

Ishimaru, Yasuji ^{[1
]}

Ono, Tomomichi ^{[1
]}

Sagara, Katsurou ^{[1
]}

Narahara, Shinji ^{[1
]}

Matsmoto, Tamami ^{[1
]}

Hirose, Eiji ^{[1
]}

Yamaguchi, Yasuo ^{[1
]}

机构：

[1] Kumamoto Hlth Sci Univ, Dept Med Technol, Kumamoto 8615598, Japan

来源：

BLOOD CELLS MOLECULES AND DISEASES | 2015年 / 54卷 / 02期

关键词：

Monocyte; Neutrophil elastase; Protein kinase C; Tissue factor; Disseminated intravascular coagulation; PROTEIN-KINASE-C; PERIPHERAL-BLOOD MONOCYTES; FACTOR EXPRESSION; PHORBOL ESTER; INHIBITION; ALPHA; INDUCTION; DIFFERENTIATION; ENDOTOXIN; ISOFORMS;

D O I：

10.1016/j.bcmd.2014.10.005

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background: Monocytes and neutrophils are activated during disseminated intravascular coagulation. Tissue factor, the main initiator of coagulation, is expressed by monocytes, while elastase is released by neutrophils. Aims: This study investigated tissue factor production by peripheral monocytes after stimulation with human neutrophil elastase. Methods: Tissue factor mRNA levels were investigated by the reverse transcriptase-polymerase chain reaction and tissue factor protein production was assessed by western blotting when monocytes were exposed to neutrophil elastase with or without preincubation using various inhibitors. Results: Neutrophil elastase upregulated tissue factor mRNA and protein levels in monocytes. Both U73122 (phospholipase C inhibitor) and TMB-8 (intracellular calcium antagonist) prevented the upregulation of tissue factor mRNA. SB203580 (p38 mitogen-activated protein kinase inhibitor) suppressed this response, but PD98059 (extracellular signal-regulated kinase inhibitor) did not. Ro-318425 (ATP-competitive and selective protein kinase C (PKC) inhibitor) and Go 6976 (inhibitor of conventional PKCs and PKC mu) blocked the upregulation of tissue factor mRNA expression. Go 6983 (broad-spectrum PKC inhibitor) and CGP 4125 (staurosporine analog) partially attenuated it, as did a PKC theta/delta inhibitor. Conclusions: Neutrophil elastase mainly enhances tissue factor production by monocytes via the phospholipase C/conventional PKC/p38 MAPK pathway, although a novel PKC is also involved. (C) 2014 Elsevier Inc. All rights reserved.

引用

页码：206 / 209

页数：4

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