Zhao Xiurong, Kruzel Marian, Aronowski Jaroslaw
Department of Neurology UTHealth Neuroscience, University of Texas Health Science Center at Houston, McGovern Medical School, Houston, TX 77030, USA.
Department of Integrative Biology and Pharmacology, University of Texas Health Science Center at Houston, McGovern Medical School, Houston, TX 77030, USA.
Biochem Cell Biol. 2021 Feb;99(1):97-101. doi: 10.1139/bcb-2020-0116. Epub 2020 Sep 4.
In this minireview we discuss 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 contents, including LTF. LTF is an iron-binding glycoprotein that binds Fe with high affinity. Unlike other iron-binding proteins, LTF can retain Fe at the low pH associated with inflamed tissue. LTF's ability to sequester Fe is of particular importance to ICH pathogenesis, because large quantities of free iron, which is pro-oxidative and pro-inflammatory, are generated in the ICH-affected brain owing to blood hemolysis. LTF delivered to ICH-affected brain, either as a therapeutic agent or through infiltrated polymorphonuclear neutrophils (cells containing high levels of LTF), could limit the pathogenesis of ICH. LTF is a protein with a high isoelectric point (8.7), a property that enables it to bind 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 facilitate 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.
在本综述中，我们讨论了乳铁蛋白（LTF）在脑出血（ICH）后血肿解毒中的作用。脑出血后，中性粒细胞进入受脑出血影响的脑内，在那里它们释放包括乳铁蛋白在内的各种颗粒成分。乳铁蛋白是一种铁结合糖蛋白，能与铁高亲和力结合。与其他铁结合蛋白不同，乳铁蛋白能在与炎症组织相关的低pH值环境下保留铁。乳铁蛋白螯合铁的能力对脑出血的发病机制尤为重要，因为由于血液溶血，在受脑出血影响的脑内会产生大量具有促氧化和促炎作用的游离铁。作为一种治疗剂或通过浸润的多形核中性粒细胞（含有高水平乳铁蛋白的细胞）输送到受脑出血影响的脑内的乳铁蛋白，可能会限制脑出血的发病机制。乳铁蛋白是一种具有高电点（8.7）的蛋白质，这一特性使其能够与带负电荷的凋亡细胞或蛋白质结合。在这里，乳铁蛋白可以作为一种桥接分子，将凋亡细胞与小胶质细胞/巨噬细胞膜上的乳铁蛋白受体连接起来，以促进凋亡细胞和受损红细胞的胞葬作用/红细胞吞噬作用。因此，通过螯合铁和促进胞葬作用，乳铁蛋白可能有助于脑出血后血肿的解毒以及血肿/炎症的消退。
