嗜酸性粒细胞相关疾病的实验建模。
Experimental Modeling of Eosinophil-Associated Diseases.
机构信息
John W. Deming Department of Medicine, Section of Pulmonary Diseases, Tulane Eosinophilic Disorder Center (TEDC), Tulane University School of Medicine, New Orleans, LA, USA.
出版信息
Methods Mol Biol. 2021;2241:275-291. doi: 10.1007/978-1-0716-1095-4_21.
Eosinophils are an important subtype of leukocytes derived from bone marrow multipotent hematopoietic stem cells and represent about 1% of leukocytes in circulating blood. In homeostatic conditions, eosinophils reside in the intestine to maintain the balance of immune responses by communicating with gut microbes without causing inflammation. However, under the stressed or diseased condition, eosinophils degranulate, releasing their granule-derived cytotoxic proteins that are involved in inflammatory responses. Various eosinophil-associated inflammatory diseases are eosinophilic esophagitis (EoE), eosinophilic gastroenteritis (EG), and eosinophilic colitis (EC), together called EGID, asthma, hypereosinophilic syndrome, and eosinophilic pneumonia (EP). Eosinophil degranulation results in the release of their four toxic proteins [major basic protein (MBP), eosinophil cationic protein (ECP), eosinophil peroxidase (EPO), and eosinophil-derived neurotoxin (EDN)] which promote disease pathogenesis. Pancreatitis is the inflammatory disease of the pancreas that arises due to blockage of the pancreatic duct, trypsinogen mutation, alcohol consumption, and repeated occurrence of pancreatitis leading to chronic pancreatitis (CP); subsequently some CP patients may also develop pancreatic cancer. The presence of eosinophils is now shown in various case reports with acute, recurrent acute, and chronic pancreatitis and pancreatic cancer indicating the role of eosinophils in the pathogenesis of various pancreatic inflammatory disorders. However, the details of eosinophil accumulation during pancreatic diseases are not well explored and need further attention. Overall, the chapter provides the current understanding of reported eosinophils associated with inflammatory diseases like EGID diseases, asthma, and pancreatic disorders, i.e., acute, chronic pancreatitis, and pancreatic cancer. This knowledge will be helpful for future studies to develop novel treatment options for the eosinophils associated diseases. Therefore, more efforts are needed to perform preclinical and clinical studies in this field for the successful development of eosinophil-targeting treatments for a variety of eosinophil-associated diseases.
嗜酸性粒细胞是一种重要的白细胞亚型,起源于骨髓多能造血干细胞,约占循环血液中白细胞的 1%。在稳态条件下,嗜酸性粒细胞驻留在肠道中,通过与肠道微生物交流来维持免疫反应的平衡,而不会引起炎症。然而,在应激或患病状态下,嗜酸性粒细胞脱颗粒,释放其颗粒衍生的细胞毒性蛋白,参与炎症反应。各种与嗜酸性粒细胞相关的炎症性疾病包括嗜酸性食管炎 (EoE)、嗜酸性胃肠炎 (EG) 和嗜酸性结肠炎 (EC),统称为 EGID,哮喘、高嗜酸性粒细胞综合征和嗜酸性肺炎 (EP)。嗜酸性粒细胞脱颗粒导致其四种毒性蛋白[主要碱性蛋白 (MBP)、嗜酸性粒细胞阳离子蛋白 (ECP)、嗜酸性粒细胞过氧化物酶 (EPO) 和嗜酸性粒细胞衍生的神经毒素 (EDN)]的释放,促进疾病的发病机制。胰腺炎是胰腺的炎症性疾病,由于胰管阻塞、胰蛋白酶原突变、酒精摄入和反复发生胰腺炎导致慢性胰腺炎 (CP);随后一些 CP 患者也可能发展为胰腺癌。目前在各种急性、复发性急性和慢性胰腺炎以及胰腺癌的病例报告中都显示有嗜酸性粒细胞的存在,表明嗜酸性粒细胞在各种胰腺炎症性疾病的发病机制中起作用。然而,嗜酸性粒细胞在胰腺疾病中的积累的细节尚不清楚,需要进一步关注。总的来说,本章提供了目前对 EGID 疾病、哮喘和胰腺疾病等炎症性疾病中嗜酸性粒细胞的认识,即急性、慢性胰腺炎和胰腺癌。这一知识将有助于未来研究开发针对与嗜酸性粒细胞相关的疾病的新的治疗方法。因此,需要在这一领域进行更多的临床前和临床研究,以成功开发针对各种与嗜酸性粒细胞相关疾病的嗜酸性粒细胞靶向治疗方法。