Kew Richard R
Department of Pathology, Stony Brook Cancer Center, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY, United States.
Front Endocrinol (Lausanne). 2019 Jul 10;10:470. doi: 10.3389/fendo.2019.00470. eCollection 2019.
Neutrophils are the most abundant type of white blood cell in most mammals including humans. The primary role of these cells is host defense against microbes and clearance of tissue debris in order to facilitate wound healing and tissue regeneration. The recruitment of neutrophils from blood into tissues is a key step in this process and is mediated by numerous different chemoattractants. The neutrophil migratory response is essential for host defense and survival, but excessive tissue accumulation of neutrophils is observed in many inflammatory disorders and strongly correlates with disease pathology. The vitamin D binding protein (DBP) is a circulating multifunctional plasma protein that can significantly enhance the chemotactic activity of neutrophil chemoattractants both and . Recent studies using DBP deficient mice showed that DBP plays a larger and more central role during inflammation since it induces selective recruitment of neutrophils, and this cofactor function is not restricted to C5a, as prior studies indicated, but can enhance chemotaxis to many chemoattractants. DBP also is an extracellular scavenger for actin released from damaged/dead cells and formation of DBP-actin complexes is an immediate host response to tissue injury. Recent evidence indicates that DBP bound to G-actin, and not free DBP, functions as an indirect but essential cofactor for neutrophil migration. DBP-actin complexes always will be formed regardless of what initiated an inflammation, since release of actin from damaged cells is a common feature in all types of injury and DBP is abundant and ubiquitous in all extracellular fluids. Indeed, these complexes have been detected in blood and tissue fluids from both humans and experimental animals following various forms of injury. The published data strongly supports the premise that DBP-actin complexes are the functional neutrophil chemotactic cofactor that enhances neutrophil chemotaxis and augments neutrophilic inflammation . This review will assess the fundamental role of DBP in neutrophilic inflammation and injury.
中性粒细胞是包括人类在内的大多数哺乳动物中数量最多的白细胞类型。这些细胞的主要作用是抵御微生物入侵宿主以及清除组织碎片，以促进伤口愈合和组织再生。中性粒细胞从血液募集到组织中是这一过程的关键步骤，并且由多种不同的趋化因子介导。中性粒细胞的迁移反应对于宿主防御和生存至关重要，但在许多炎症性疾病中观察到中性粒细胞在组织中过度积聚，并且与疾病病理密切相关。维生素D结合蛋白（DBP）是一种循环的多功能血浆蛋白，它可以显著增强中性粒细胞趋化因子的趋化活性。最近使用DBP缺陷小鼠的研究表明，DBP在炎症过程中发挥着更大且更核心的作用，因为它诱导中性粒细胞的选择性募集，并且这种辅助因子功能并不局限于C5a（如先前研究所表明的），而是可以增强对许多趋化因子的趋化作用。DBP还是受损/死亡细胞释放的肌动蛋白的细胞外清除剂，DBP-肌动蛋白复合物的形成是宿主对组织损伤的即时反应。最近的证据表明，与G-肌动蛋白结合的DBP（而非游离的DBP）作为中性粒细胞迁移的间接但必不可少的辅助因子发挥作用。无论引发炎症的原因是什么，都会形成DBP-肌动蛋白复合物，因为受损细胞释放肌动蛋白是所有类型损伤的共同特征，并且DBP在所有细胞外液中都大量存在且普遍存在。事实上，在各种形式的损伤后，已在人类和实验动物的血液和组织液中检测到这些复合物。已发表的数据有力地支持了这样一个前提，即DBP-肌动蛋白复合物是功能性中性粒细胞趋化辅助因子，可增强中性粒细胞趋化作用并加剧嗜中性粒细胞炎症。本综述将评估DBP在嗜中性粒细胞炎症和损伤中的基本作用。
