PECAM-1 Protects against DIC by Dampening Inflammatory Responses via Inhibiting Macrophage Pyroptosis and Restoring Vascular Barrier Integrity.
Journal: 2020/May - Translational research : the journal of laboratory and clinical medicine
ISSN: 1878-1810
Abstract:
Disseminated intravascular coagulation (DIC) is a frequent complication of sepsis that affects patient outcomes due to accompanying thrombo-inflammation and microvascular permeability changes. Platelet endothelial cell adhesion molecule-1 (PECAM-1), a cellular adhesion and signaling receptor that is expressed on both hematopoietic and endothelial cells, plays an important anti-inflammatory role in acute and chronic inflammatory disease models. Little is known, however, about role and mechanism of PECAM-1 in septic DIC. Here, we investigated whether PECAM-1 might play a protective role in hindering the development of septic DIC. Plasma levels of soluble PECAM-1 were markedly elevated in septic patients that developed DIC, with a correspondingly poorer outcome. PECAM-1 knockout exhibited more severe DIC and poorer outcome in the LPS induced- and cecal ligation and puncture-induced DIC model, which could be alleviated by tissue factor inhibitor. This phenomenon seemed to be equally linked to PECAM-1 expression by both endothelial and blood cells. Furthermore, PECAM-1 was found to exert its protective effect on developing septic DIC by the following two distinct mechanisms: the inhibition of macrophage pyroptosis and the acceleration of the restoration of the endothelial cell barrier. Taken together, these results implicate PECAM-1 as a potentially attractive target for the development of novel therapeutics to manage and treat septic DIC.
Relations:
Citations
(1)
Diseases
(1)
Conditions
(2)
Drugs
(1)
Chemicals
(3)
Genes
(2)
Processes
(3)
Anatomy
(4)
Affiliates
(1)
Similar articles
Articles by the same authors
Discussion board
Collaboration tool especially designed for Life Science professionals.Drag-and-drop any entity to your messages.