Thrombin Promotes Macrophage Polarization into M1-Like Phenotype to Induce Inflammatory Responses

Thrombosis and Haemostasis
Mercedes López-ZambranoKlaus T Preissner

Abstract

Despite strong evidence supporting the cellular interplay between haemostasis and innate immunity, humoral connections between blood coagulation and the behavior of inflammatory macrophages are not well understood. In this study, we investigated changes in gene expression of selected cytokines and chemokines and their secretion profiles following thrombin stimulation of murine macrophages. Thrombin promoted differentiation of macrophages into an M1-like phenotype that was associated with the expression of classical pro-inflammatory markers. The cellular actions of thrombin on macrophages were mediated in part by protease-activated receptor-1 (PAR-1) and were dependent on phosphoinositide 3-kinase/AKT and nuclear factor-κB. Moreover, heat-denatured thrombin stimulated the secretion of some pro-inflammatory mediators to the same magnitude indicating that different receptors transmit cellular signals of enzymatically active thrombin and nonactive thrombin, the latter remaining so far undefined. Finally, pretreatment of macrophages with thrombin resulted in tolerance against secondary stimulation by lipopolysaccharide with regard to expression of tumor necrosis factor-α. These results provide new insights into the molecular link be...Continue Reading

Citations

Jan 8, 2021·Metabolic Brain Disease·Kelley R JordanNorah G Verbout
Jun 29, 2021·Frontiers in Cardiovascular Medicine·Lulu AnPoornima Venkat

❮ Previous
Next ❯

Related Concepts

Related Feeds

Blood Coagulation Signaling Pathways

Coagulation is the process by which a blood clot is formed. This process includes both the formation of a platelet plug as well as a cascade of clotting factors resulting in the formation of fibrin strands. Find the latest research on coagulation signaling pathways here.

Blood Clotting Disorders

Thrombophilia includes conditions with increased tendency for excessive blood clotting. Blood clotting occurs when the body has insufficient amounts of specialized proteins that make blood clot and stop bleeding. Here is the latest research on blood clotting disorders.

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.