FPR2/ALX is a therapeutic target for the resolution of thrombo‐inflammation

Abstract

Patients with Sickle Cell Disease (SCD) are more susceptible to thrombotic events, in which leukocytes, platelets and erythrocytes have all been implicated in the pathogenesis. However, the underlying mechanisms promoting a pro‐coagulant and pro‐thrombotic phenotype in SCD (especially in the brain) are still unknown. The causes for the SCD phenotype may relate to a well‐established link between thrombosis and inflammation i.e. inflammation can beget local thrombosis, and thrombosis can amplify inflammation. Accumulating data linking inflammation and thrombosis supports the hypothesis that anti‐inflammatory therapies may limit thrombosis and that anti‐thrombotic therapies may reduce vascular inflammation. One such target is the anti‐inflammatory and pro‐resolving endogenous mediator Annexin A1 (AnxA1) and its interaction with the Formyl Peptide Receptor (FPR) family. In humans three FPRs (FPR1, FPR2, and FPR3) regulate innate inflammatory responses. Their function has been most extensively investigated in the context of leukocyte recruitment and activation, where FPRs promote cell motility (chemotaxis) and microbicidal respiratory burst. Here we have tested the effect of targeting the AnxA1‐Fpr2/ALX pathway as a therapeutic strategy for SCD with a special focus on thrombo‐inflammation. In conclusion, our novel results demonstrate the importance of the AnxaA1/FPR2 system in effecting the resolution of SCD associated cerebral thrombo‐inflammation and may therefore provide a novel anti‐thrombo‐inflammatory therapeutic target.Support or Funding InformationNIH/NHLBI (HL125572‐01A1)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.