Sadowska A M, van Overveld F J, Luyten C, Germonpré P, De Backer W A
Department of Respiratory Medicine, Antwerp Metabolic Research Unit, University of Antwerp (UIA), Universiteitsplein 1, 2610 Antwerpen-Wilrijk, Belgium.
Inflamm Res. 2004 Apr;53(4):143-9. doi: 10.1007/s00011-003-1237-x. Epub 2004 Mar 18.
The increase in adhesion molecule expression during the initial phase of inflammation leads to transmigration of neutrophils. Inhibition of this transmigration could decrease inflammatory response and tissue damage.
Uptake of fluorescein-labelled oligonucleotides, expression of ICAM-1 and neutrophil migration were studied using the bilayer of epithelial (H292) and endothelial (ECV-304) cell lines and neutrophils from peripheral blood of healthy volunteers.
The inhibition of ICAM-1 expression was time dependent for both cell lines, with inhibition of more than 50% after 48 h. Antisense oligos inhibited transmigration already after 4 h of incubation (6.6 +/- 2.5% versus 18.6 +/- 2.5% inhibition, p < 0.01). Antisense was more effective in preventing fMLP-induced neutrophil migration than ICAM-1 antibodies (88 +/- 3.8% versus 67 +/- 7% inhibition, p = 0.02).
Antisense oligos cause a decrease in ICAM-1 expression and inhibit transmigration of neutrophils. However the effectiveness of antisense is higher than monoclonal antibodies, neither of them is able to block the migration completely. This suggests the existence of ICAM-1 independent mechanisms that are responsible for migration.
炎症初始阶段黏附分子表达增加会导致中性粒细胞迁移。抑制这种迁移可减少炎症反应和组织损伤。
使用上皮细胞系（H292）和内皮细胞系（ECV - 304）双层培养物以及健康志愿者外周血中的中性粒细胞，研究荧光素标记寡核苷酸的摄取、细胞间黏附分子 - 1（ICAM - 1）的表达及中性粒细胞迁移。
两种细胞系中ICAM - 1表达的抑制均呈时间依赖性，48小时后抑制率超过50%。反义寡核苷酸孵育4小时后即抑制迁移（抑制率为6.6±2.5%，而对照组为18.6±2.5%，p<0.01）。在阻止fMLP诱导的中性粒细胞迁移方面，反义寡核苷酸比ICAM - 1抗体更有效（抑制率分别为88±3.8%和67±7%，p = 0.02）。
反义寡核苷酸可使ICAM - 1表达降低并抑制中性粒细胞迁移。然而，反义寡核苷酸的有效性高于单克隆抗体，两者均不能完全阻断迁移。这表明存在负责迁移的ICAM - 1非依赖性机制。
