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Under homeostasis, destruction of aged RBCs is usually an unrecognized event that takes place in macrophages of splenic and hepatic sinusoids ( Heme is a well-known pro-oxidant that feature reliesat least in parton the ability of heme iron to catalize the generation of hydroxyl-radicals in the Fenton reaction, due to its capability of acting as both an electron donor and an acceptor ( 2 will generate more peroxyl radicals, thus amplifying free radical reactions ( Besides being a pro-oxidant, three lines of evidence indicated that heme is an inflammatory molecule with unique properties: (i) sterile intra or extra vascular hemolysis cause inflammation, that is controlled by Hx and heme oxygenase-1 (HO-1) ( in vitro acting as a chemoatractant, inducing cytokine production, ROS generation, and cell death ( Growing evidence suggest that besides labile heme other Hb-related DAMPs e.g., metHb, ferrylHb as well as covalently crosslinked Hb multimers can be considered as alarmins ( Hb Inside of the RBCs Hb, the major oxygen-transport protein consist of 2 different subunits, and , that compose a 22 tetrahedron

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Huang WC, Tsai TH, Huang CJ et al (2015) Inhibitory effects of wild bitter melon leaf extract on Propionibacterium acnes-induced skin inflammation in mice and cytokine production in vitro