| First Author | Wang B | Year | 2019 |
| Journal | Biochem Biophys Res Commun | Volume | 518 |
| Issue | 3 | Pages | 409-415 |
| PubMed ID | 31451224 | Mgi Jnum | J:291384 |
| Mgi Id | MGI:6443918 | Doi | 10.1016/j.bbrc.2019.07.060 |
| Citation | Wang B, et al. (2019) Plasma kallikrein contributes to ambient particulate matter-induced lung injury. Biochem Biophys Res Commun 518(3):409-415 |
| abstractText | 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 PM2.5-induced lung injury. Using TALEN technology, we generated a new mouse strain lacking the gene for pKal. In PM2.5-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 PM2.5-treated Klkb1(-/-) mice. Plasma thrombin-antithrombin (TAT) complex levels were significantly decreased in PM2.5-treated Klkb1(-/-) mice. PM2.5 induces pKal activation, HK cleavage and bradykinin production. PM2.5-induced HK cleavage in plasma was completely blocked by a Kal inhibitor, as well as in pKal-deficient plasma. PM2.5 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 PM2.5 and the activated Kal plays an important role in PM2.5-induced lung injury. |
