PMID- 31451224
OWN - NLM
STAT- MEDLINE
DCOM- 20200608
LR  - 20200608
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 518
IP  - 3
DP  - 2019 Oct 20
TI  - Plasma kallikrein contributes to ambient particulate matter-induced lung injury.
PG  - 409-415
LID - S0006-291X(19)31414-7 [pii]
LID - 10.1016/j.bbrc.2019.07.060 [doi]
AB  - Particulate matter (PM) is a key component of air pollutants and is associated 
      with mortality of cardiovascular and respiratory diseases. PM-induced tissue 
      injury involves inflammation and coagulation. Plasma prekallikrein (pKal), along 
      with coagulation factor XII (FXII) and high-molecular-weight kininogen (HK), form 
      the plasma kallikrein-kinin system (KKS), a component of the innate immune 
      response that generates proinflammatory products in response to injury. When the 
      KKS proteins contact with activation surface such as negatively charged 
      molecules, this system becomes activated. Activated kallikrein (Kal) activates 
      FXII to initiate the intrinsic coagulation pathway, and cleaves HK to release 
      bradykinin to enhance vascular permeability and systemic inflammation. In his 
      study we determined the role of plasma pKal in the PM(2.5)-induced lung injury. 
      Using TALEN technology, we generated a new mouse strain lacking the gene for 
      pKal. In PM(2.5)-induced lung injury model, Klkb1(-/-) mice exhibited a decrease 
      in total protein, cells numbers in bronchoalveolar lavage fluid (BALF) and 
      histologic lung injury score. The TNF-alpha and IL-6 levels in BALF were 
      significantly decreased in PM(2.5)-treated Klkb1(-/-) mice. Plasma 
      thrombin-antithrombin (TAT) complex levels were significantly decreased in 
      PM(2.5)-treated Klkb1(-/-) mice. PM(2.5) induces pKal activation, HK cleavage and 
      bradykinin production. PM(2.5)-induced HK cleavage in plasma was completely 
      blocked by a Kal inhibitor, as well as in pKal-deficient plasma. PM(2.5) markedly 
      induced thrombin generation in human plasma and wild-type mouse plasma, which was 
      inhibited by both blockade and deficiency of pKal. Taken together, plasma pKal is 
      activated by PM(2.5) and the activated Kal plays an important role in 
      PM(2.5)-induced lung injury.
CI  - Copyright (c) 2019 Elsevier Inc. All rights reserved.
FAU - Wang, Bo
AU  - Wang B
AD  - Cyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, 
      State Key Laboratory of Radiation Medicine and Protection, Soochow University, 
      Suzhou, China.
FAU - Yan, Xiaofeng
AU  - Yan X
AD  - Cyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, 
      State Key Laboratory of Radiation Medicine and Protection, Soochow University, 
      Suzhou, China.
FAU - Chen, Fengwu
AU  - Chen F
AD  - Cyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, 
      State Key Laboratory of Radiation Medicine and Protection, Soochow University, 
      Suzhou, China.
FAU - Yang, Aizhen
AU  - Yang A
AD  - Cyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, 
      State Key Laboratory of Radiation Medicine and Protection, Soochow University, 
      Suzhou, China.
FAU - Lu, Yi
AU  - Lu Y
AD  - Wuhan Thalys Medical Technology Inc, Wuhan, China.
FAU - Wu, Yi
AU  - Wu Y
AD  - Cyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, 
      State Key Laboratory of Radiation Medicine and Protection, Soochow University, 
      Suzhou, China; The Sol Sherry Thrombosis Research Center, Temple University 
      School of Medicine, Philadelphia, PA, 19140, USA. Electronic address: 
      yiwu@temple.edu.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190823
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Particulate Matter)
RN  - EC 3.4.21.34 (Plasma Kallikrein)
SB  - IM
MH  - Animals
MH  - *Blood Coagulation
MH  - Gene Deletion
MH  - Humans
MH  - Inflammation/blood/*etiology/genetics/immunology
MH  - Lung Injury/blood/*etiology/genetics/immunology
MH  - Mice
MH  - Mice, Knockout
MH  - Particulate Matter/*adverse effects/immunology
MH  - Plasma Kallikrein/analysis/genetics/*immunology
OTO - NOTNLM
OT  - Coagulation
OT  - Inflammation
OT  - Lung injury
OT  - Particulate matter 2.5
OT  - Plasma kallikrein
EDAT- 2019/08/28 06:00
MHDA- 2020/06/09 06:00
CRDT- 2019/08/28 06:00
PHST- 2019/07/06 00:00 [received]
PHST- 2019/07/18 00:00 [accepted]
PHST- 2019/08/28 06:00 [pubmed]
PHST- 2020/06/09 06:00 [medline]
PHST- 2019/08/28 06:00 [entrez]
AID - S0006-291X(19)31414-7 [pii]
AID - 10.1016/j.bbrc.2019.07.060 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2019 Oct 20;518(3):409-415. doi: 
      10.1016/j.bbrc.2019.07.060. Epub 2019 Aug 23.