Heme Interferes With Complement Factor I-Dependent Regulation by Enhancing Alternative Pathway Activation.

ABSTRACT: Hemolysis, as a result of disease or exposure to biomaterials, is characterized by excess amounts of cell-free heme intravascularly and consumption of the protective heme-scavenger proteins in plasma. The liberation of heme has been linked to the activation of inflammatory systems, including the complement system, through alternative pathway activation. Here, we investigated the impact of heme on the regulatory function of the complement system. Heme dose-dependently inhibited factor I-mediated degradation of soluble and surface-bound C3b, when incubated in plasma or buffer with complement regulatory proteins. Inhibition occurred with factor H and soluble complement receptor 1 as co-factors, and the mechanism was linked to the direct heme-interaction with factor I. The heme-scavenger prote

SUBMITTER: Gerogianni A 

PROVIDER: S-EPMC9354932 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature