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Recently it was reported that heme is a potent inducer of trained immunity in monocytes and macrophages both in vitro and in vivo (Figure 3) ( in vivo resulting that the outcome of heme pretreatment largely depends on the experimental conditions ( Complement Activation and the Thromboinflammatory Loop Originally the complement system has been considered as a simple mechanism to induce bacterial lysis

These effects are partially abrogated by inhibitors of adenosine receptor activation, AKT, ERK, and AMPK phosphorylation

OkazakiTSuzukamoYMiyatakeMKomatsuRYaekashiwaMNiheiMet al

doi: 10.1667/RADE-19-00012 122 GmezFGCFernndezDMPardo-MonteroNGSchllerJGaspariniAVanreuselAet al

Toxicol Appl Pharmacol, 21