Fig. 5.

Illustration of HFM-induced inflammation. The membrane first induces autoactivation of FXII to FXIIa. FXIIa activates HK-bound PK to K, which cleaves HK to BK and induces an inflammatory response. a The contact activation of coagulation and complement activation can lead to leukocyte activation, and the activated leukocytes can secrete ROS, TF, pro-inflammatory cytokines, and enzymes. b The principal mechanism leading to complement activation on HFM is the binding of ficolin-2 and MBL to the membrane, resulting in LP activation. Simultaneously, properdin and/or C3b bind to the membrane, resulting in AP activation. Surface functional groups on HFM, such as hydroxyl group, can also contribute to AP activation. c) Frustrated phagocytosis is thought to be the primary initiator of macrophage fusion, leading to the formation of multinucleated FBGCs, which are characteristic of the foreign body reaction. Abbreviations: PK prekallikrein, K kallikrein, HK high-molecular-weight kininogen, BK bradykinin, FBGC foreign body giant cells, TF tissue factor, IgG immunoglobulin G, ROS reactive oxygen species, RNS reactive nitrogen species, LP lectin pathway, AP alternative pathway