Leukotriene B4(LTB4) is lipid mediator derived from membrane phospholipids during the process of inflammation, having many roles(ie; inducer of chemotaxis, the production of nitric oxide, transepithelial migration of neutrophil). The major activities of LTB4 include the recruitment and activation of leukocytes, suggesting that it may involve the process for transendothelial migration of nuclear cells in bone marrow environment. Reactive Oxygen Species (ROS) have a cell signaling roles that are involved in signal transduction cascades of numerous growth factor-, cytokine-, and hormone-mediated pathways, and regulate many biological systems. In this present study, we focused on the role of LTB4 and ROS on transmigration of bone marrow nuclear cells across endothelial or stromal cell monolayer.
MS-5, murine stromal cell line cells, or bEnd.3, murine microvascular cell line cells, were grown to confluence on microporous transwell membrane. Murine marrow cells were placed on top of the prepared transwell membrane. The transwells were then seated in wells containing media and LTB4 with or without pretreatment of N-acetylcysteine(NAC), an oxygen free radical scavenger, or diphenylene iodonium(DPI), an inhibitor of NADPH oxidase-like flavoproteins. Cells that migrated through the stromal or endothelial layer into the wells were assayed for transendothelial migration.
The numbers of migrated bone marrow nuclear cells through the bEnd.3 were increased by treatment of LTB4(control, 12.5±0.2%; 50nM, 22.7±0.9%; 100nM, 44.3±1.4%; 200 nM, 36.3±0.9%; p<0.05). The numbers of migrated bone marrow nuclear cells through the MS-5 were also increased by treatment of LTB4(control, 11.0±0.9%; 50nM, 25.7±0.9%; 100nM, 35.8±1.8%; 200nM, 32.1±0.9%; p<0.05). However, increasing effect of LTB4 to the transmigration of bone marrow nuclear cells through the MS-5 or bEnd.3 were inhibited by pretreatment of NAC or DPI.
Through our data, it is suggested that LTB4 could induce the transmigration of bone marrow nuclear cells and ROS might be involved on the transendothelial migration of bone marrow nuclear cells by LTB4. It would be very interesting to test the effects of LTB4 and ROS on stem cell mobilization and homing in the future.
Dieulafoy's disease is the vascular anomaly characterized by the presence of arteries of persistent large caliber in the submucosa, and in some instances, the mucosa, typically with a small, overlying mucosal defect. Only a few cases of this lesion occuring in the bronchial system have been reported to date. The etiology of Dieulafoy's disease is still unclear, but chronic bronchial injury and/or congenital vascular malformation have been postulated. We encountered a case of bronchial Dieulafoy's disease that developed in a 69-year-old woman who had been treated for pulmonary tuberculosis for 4 months. Her chief complaint was hemoptysis and the bronchoscopic finding showed an intrabronchial protruding lesion produced by the arteries beneath the bronchial mucosa of the anterior segment of right upper lobe. She has been well after the surgical resection of right upper lobe.
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