FIG. 1.

A model depicting the involvement of extracellular hemoglobin in host cell innate immune responses via Toll-like receptors (TLRs) and other membrane-bound receptors. Extracellular hemoglobin (Hb) released by hemolysis is normally endocytosed by Hb scavengers, such as haptoglobin, scavenger receptor class B type 1 (SR-B1), and CD163 for intracellular degradation. However, excessive levels of extracellular hemoglobin produced under abnormal conditions, overwhelms the Hb scavengers and membrane receptors. The cell-free Hb binds to pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs). The Hb-PAMP and the Hb-DAMP complexes are recognized by pattern recognition receptors, such as TLRs in various immune cells, triggering proinflammatory responses.