Lactoferrin and hematoma detoxification after intracerebral hemorrhage

This review discusses the role of lactoferrin (LTF) in detoxifying hematoma after intracerebral hemorrhage (ICH). Subsequent to ICH, neutrophils enter the ICH-affected brain, where they release various granule content, including LTF. LTF is an iron-binding glycoprotein that binds Fe3+ with high affinity. Unlike other iron binding proteins, LTF can retain Fe3+ at the low pH associated with inflamed tissue. LTF's ability to sequester Fe3+ is of particular importance to ICH pathogenesis, as large quantities of free iron, which is pro-oxidative and pro-inflammatory are generated in the ICH-affected brain due to blood hemolysis. LTF delivered to ICH-affected brain, either as therapeutic agent or through infiltrated PMNs (cells containing high levels of LTF), could benefit ICH pathogenesis. LTF is a protein with a high isoelectric point (8.7), property that enables it to binding to negatively charged apoptotic cells or proteins. Here, LTF could act as a bridging molecule that couples the apoptotic cells to LTF receptors on the cellular membranes of microglia/macrophages to facilitates the efferocytosis/erythrophagocytosis of apoptotic cells and damaged red blood cells. Thus, by virtue of sequestrating iron and facilitating efferocytosis, LTF may contribute to hematoma detoxification and hematoma/inflammation resolution after ICH.