- 细胞因子及免疫学检验
- 崔天盆
- 777字
- 2020-08-29 08:36:50
四、白细胞介素-8的生物学功能
(一)趋化和激活中性粒细胞
IL-8的趋化和激活中性粒细胞作用无明显种属特异性,动物腹腔或静脉注射IL-8可引起外周血中性粒细胞增加。IL-8可促使中性粒细胞形态改变,促进脱颗粒,激活中性粒细胞并使其产生呼吸爆发(respiratory burst)。局部注射IL-8可趋化中性粒细胞,并刺激中性粒细胞产生白三烯B4(LTB4);IL-8还可诱导中性粒细胞上调Mac-1,促进中性粒细胞黏附到内皮细胞和内皮下基质。
(二)趋化嗜碱性粒细胞
IL-8可趋化嗜碱性粒细胞发生胞吐作用(exocytosis),并刺激释放组胺(histamine),与速发超敏反应有关。此外,IL-8还可刺激GM-CSF和IL-5预先处理的嗜酸性粒细胞脱颗粒。
(三)趋化淋巴细胞
IL-8在单核细胞存在的情况下可趋化CD4 +T细胞和CD8 +T细胞。局部注射IL-8可使局部淋巴结T细胞明显增多,同时,IL-8还可趋化IL-2活化的NK细胞。
五、白细胞介素-8与疾病
(一)IL-8与急性炎症
IL-8在炎症情况下参与中性粒细胞招募和脱颗粒,如作为牙周炎(periodontitis)的促炎性介质。败血症休克、急性脑膜炎患者血清中IL-8显著升高。
(二)IL-8与慢性炎症
肺囊性纤维化时,IL-8水平升高,招募中性粒细胞至肺组织中,导致促炎性细胞因子释放。胃炎、酒精性肝炎患者血清中IL-8明显高于正常对照组。因此,抗IL-8抗体用于治疗囊性纤维化等炎性疾病。
(三)IL-8与自身免疫性疾病
类风湿关节炎患者关节滑液中含有IL-8,IL-8可诱导中性粒细胞促进软骨降解,引起软骨损伤。检测分析发现,银屑病(psoriasis)患者的皮屑中含有IL-8。同时,炎性肠病患者血清中IL-8水平明显高于正常对照组。
(四)IL-8在肿瘤细胞微环境中的作用
1.促进肿瘤细胞增殖
肿瘤组织及癌旁组织IL-8表达可诱导肿瘤细胞内上述多条信号转导通路活化,导致肿瘤细胞增殖和存活能力增强。Kamohara等研究发现,胰腺癌中IL-8过表达,可促进肿瘤细胞增殖;Mac Manus等证实前列腺癌组织中的IL-8可促进癌细胞周期素D1和细胞周期素B的表达,这2种周期素是细胞从G1期向S期转变的关键因素,它们的高表达表明IL-8有促进前列腺癌细胞增殖的作用。
2.促进肿瘤组织中血管的形成
研究表明,肿瘤来源的IL-8可调节肿瘤血管内皮细胞的生长状态及血管壁的通透性,促进肿瘤组织血管的生成,诱导肿瘤内部中性粒细胞的趋化渗透。Merritt等运用小RNA干扰技术抑制卵巢癌细胞IL-8表达,显著降低癌组织中微血管的密度;Huang等通过特异性抗体抑制瘤内IL-8的表达可明显降低黑色素瘤的微血管形成;Karashima等在研究IL-8对膀胱癌的作用时发现,IL-8可通过激活NF-κB对血管形成发挥作用。
(五)IL-8与代谢性疾病
氧化应激可促进IL-8释放,招募炎性细胞到局部,炎性细胞又进一步加重氧化应激,IL-8在动脉粥样硬化局部炎症的恶性循环中起重要作用。
(六)IL-8与生殖病理生理
IL-8是一种属于趋化因子家族的细胞因子,近年来,人们在研究中发现,IL-8几乎参与哺乳动物的整个生殖过程如排卵、黄体形成、子宫内膜增殖、蜕膜化、胚胎着床及其生长发育等过程。许多临床研究表明,IL-8还与某些生殖病理过程有关,如子宫内膜异位症,不明原因的自然流产等。妊娠女性体内分泌高水平的IL-8,可增加后代患精神分裂症的风险,高水平IL-8降低子代对抗精神分裂症的能力。
总之,IL-8在急性炎症、慢性炎症、自身免疫性疾病、肿瘤、代谢性疾病和生殖病理生理有重要作用,检测血清IL-8对疾病病程判断、炎症消退和疾病诊断以及拮抗IL-8治疗提供重要参考。
(饶亚华 曹文操)
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