Expression of 15-lipoxygenase type-1 in human mast cells
- 作者：Magdalena Gulliksson ; Å ; sa Brunnströ ; m ; Malin Johannesson ; Linda Backman ; Gunnar Nilsson ; Ilkka Harvima ; Barbro Dahlé ; n ; Maria Kumlin ; Hans-Erik Claesson
- 关键词：Mast cell ; IL-4 ; 15-lipoxygenase ; 15-hydroxyeicosatetraenoic acid ; 15-ketoeicosatetraenoic acid
- 刊名：Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids
- 出版年：2007
- 期刊代码：18_13881981
- 类别：bio
- 出版时间：September 2007
- 卷：1771
- 期：9
- 页码：1156-1165
- 文件大小：2511 K
摘要
Mast cells play a key role in the pathophysiology of asthma. These cells exert their effector functions by releasing a variety of proinflammatory and immunoregulatory compounds. Mast cells infiltrate the bronchial epithelium and smooth muscle to a higher degree in patients with asthma compared to control subjects. 15-Lipoxygenase type-1 (15-LO-1) is a prooxidant enzyme which is expressed in asthmatic lungs leading to formation of pro- and anti-inflammatory mediators. Here we report that interleukin-4 (IL-4) induced the expression of 15-LO-1 in human cord blood derived mast cells (CBMC) as demonstrated by RT-PCR, western blot and immunocytochemistry. The major metabolite of arachidonic acid formed via the 15-LO pathway in IL-4 treated CBMC was identified as 15-ketoeicosatetraenoic acid (15-KETE, also named 15-oxo-ETE) with smaller amounts of 15-hydroxyeicosatetraenoic acid (15-HETE) as identified by HPLC and mass spectrometry (MS/MS). Furthermore, immunohistochemical stainings demonstrated the expression of 15-LO-1 in mast cells in lung and skin in vivo. Osmotic activation of CBMC with mannitol resulted in activation of the 15-LO-1 pathway. In conclusion, the expression of 15-LO-1 and release of 15-LO-1 derived products by mast cells may contribute to the role of these cells in asthma and other inflammatory diseases.