Department of Integrative Medical Sciences, Northeast Ohio Medical University College of Medicine, Rootstown, OH 44272, United States of America.
Department of Anatomy and Neurobiology, Northeast Ohio Medical University College of Medicine, Rootstown, OH 44272, United States of America.
Pharmacol Ther. 2019 Jun;198:206-219. doi: 10.1016/j.pharmthera.2019.03.001. Epub 2019 Mar 1.
Granulocytes are the major type of phagocytes constituting the front line of innate immune defense against bacterial infection. In adults, granulocytes are derived from hematopoietic stem cells in the bone marrow. Alcohol is the most frequently abused substance in human society. Excessive alcohol consumption injures hematopoietic tissue, impairing bone marrow production of granulocytes through disrupting homeostasis of granulopoiesis and the granulopoietic response. Because of the compromised immune defense function, alcohol abusers are susceptible to infectious diseases, particularly septic infection. Alcoholic patients with septic infection and granulocytopenia have an exceedingly high mortality rate. Treatment of serious infection in alcoholic patients with bone marrow inhibition continues to be a major challenge. Excessive alcohol consumption also causes diseases in other organ systems, particularly severe alcoholic hepatitis which is life threatening. Corticosteroids are the only therapeutic option for improving short-term survival in patients with severe alcoholic hepatitis. The existence of advanced alcoholic liver diseases and administration of corticosteroids make it more difficult to treat serious infection in alcoholic patients with the disorder of granulopoieis. This article reviews the recent development in understanding alcohol-induced disruption of marrow granulopoiesis and the granulopoietic response with the focus on progress in delineating cell signaling mechanisms underlying the alcohol-induced injury to hematopoietic tissue. Efforts in exploring effective therapy to improve patient care in this field will also be discussed.
粒细胞是构成固有免疫防御系统抵御细菌感染的主要吞噬细胞类型。在成人中,粒细胞来源于骨髓中的造血干细胞。酒精是人类社会中最常被滥用的物质。过量饮酒会损害造血组织,通过破坏粒细胞生成的稳态和粒细胞生成反应,损害骨髓产生粒细胞的能力。由于免疫防御功能受损,酗酒者易患传染病,特别是败血症。患有败血症和粒细胞减少症的酒精中毒患者的死亡率极高。治疗骨髓抑制的酒精中毒患者的严重感染仍然是一个主要挑战。过量饮酒还会导致其他器官系统的疾病,特别是危及生命的严重酒精性肝炎。皮质类固醇是改善严重酒精性肝炎患者短期生存率的唯一治疗选择。晚期酒精性肝病的存在和皮质类固醇的使用,使得治疗酗酒患者的严重感染更加困难,这些患者的粒细胞生成紊乱。本文综述了近年来对酒精诱导骨髓粒细胞生成和粒细胞生成反应紊乱的认识进展,重点介绍了阐明酒精对造血组织损伤的细胞信号转导机制方面的进展。还将讨论探索有效治疗方法以改善该领域患者护理的努力。