P-selectin drives complement attack on endothelium during intravascular hemolysis in TLR-4/heme-dependent manner.

ABSTRACT: Hemolytic diseases are frequently linked to multiorgan failure subsequent to vascular damage. Deciphering the mechanisms leading to organ injury upon hemolytic event could bring out therapeutic approaches. Complement system activation occurs in hemolytic disorders, such as sickle cell disease, but the pathological relevance and the acquisition of a complement-activating phenotype during hemolysis remain unclear. Here we found that intravascular hemolysis, induced by injection of phenylhydrazine, resulted in increased alanine aminotransferase plasma levels and NGAL expression. This liver damage was at least in part complement-dependent, since it was attenuated in complement C3^-/- mice and by injection of C5-blocking antibody. We evidenced C3 activation fragments' deposits on live

SUBMITTER: Merle NS 

PROVIDER: S-EPMC6442544 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature