TLR4 and infection: Ischemic tissue injury in mouse hindlimb increases both hypoxia and oxidants in the BM environment.29,172 A similar induction of oxidants in the BM was observed in infection-induced inflammation.27,154 In a hindlimb ischemia model, oxidized phospholipids, which can interfere with TLR-4 signaling, are increased in the BM, and this induction is NOX2 dependant.29,172 In these studies, NOX2 in neutrophils was identified as a source of oxidants.