Pertussis toxin transiently affects barrier integrity, organelle organization and transmigration of monocytes in a human brain microvascular endothelial cell barrier model
Pertussis toxin transiently affects barrier integrity, organelle organization and transmigration of monocytes in a human brain microvascular endothelial cell barrier model
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DOI：
10.1111/j.1462-5822.2006.00813.x
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发表时间：
2007-03-01
影响因子：
3.4
通讯作者：
Schmidt, M. Alexander
中科院分区：
文献类型：
--
作者：
Kuegler, Silke;Boecker, Kathrin;Schmidt, M. Alexander
脑病和神经系统疾病有时与百日咳杆菌引起的呼吸道感染有关。要发生这些并发症，大脑屏障必须受到损害。因此，研究了决定百日咳杆菌毒力决定因素的百日咳毒素(PT)对内皮屏障完整性的影响。以Transwell滤器上培养的人脑微血管内皮细胞作为血脑屏障的模型。PT，而不是它的B-寡聚体，诱导了内皮阻力的降低，并增加了蛋白质标记辣根过氧化物酶的通透性。此外，人类单核细胞的移行也增加，这表明PT相关的血液白细胞排泄的增强。在电子显微镜下观察PT的摄取和转运，以及溶酶体和微泡体内的蓄积。屏障完整性的破坏伴随着高尔基结构的短暂解体。有趣的是，PT诱导的效应只是短暂的，24小时后观察到屏障功能的恢复。综上所述，PT中毒导致人脑源性内皮细胞一过性细胞组织的破坏，导致屏障功能的一过性破坏。我们认为这些发现反映了与百日咳疾病相关的神经系统疾病发展的早期步骤。
Encephalopathies and neurological disorders are sometimes associated with respiratory tract infections caused by Bordetella pertussis. For these complications to occur cerebral barriers have to be compromised. Therefore, the influence of pertussis toxin (PT), a decisive virulence determinant of B. pertussis, on endothelial barrier integrity was investigated. Human brain microvascular endothelial cells cultured on Transwell filter devices were used as model for the blood brain barrier. PT, but not its B-oligomer, induced a reduction of the transendothelial resistance and enhanced the permeability for the protein marker horseradish peroxidase. Moreover, transmigration of human monocytes was also elevated suggesting a PT-associated enhancement of the diapedesis of blood leucocytes. Uptake and trafficking of PT was followed by electron microscopy via clathrin-coated pits and accumulation in lysosomes and microvesicular bodies. The breach in barrier integrity was accompanied by a transient disintegration of Golgi structures. Interestingly, PT-induced effects were only transient and restoration of barrier function was observed after 24 h. In summary, intoxication by PT causes a transient destruction of the cellular organization in human brain-derived endothelial cells resulting in a transient disruption of barrier functions. We suggest that these findings reflect early steps in the development of neurological disorders associated with pertussis disease.