Expression of 15-lipoxygenase type-1 in human mast cells.
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.
Gulliksson
Magdalena
M
The Institute of Environmental Medicine, Division of Physiology, Unit for Experimental Asthma and Allergy Research, Karolinska Institutet, P.O. Box 287, SE-171 77 Stockholm, Sweden. magdalena.gulliksson@ki.se
Brunnström
Asa
A
Johannesson
Malin
M
Backman
Linda
L
Nilsson
Gunnar
G
Harvima
Ilkka
I
Dahlén
Barbro
B
Kumlin
Maria
M
Claesson
Hans-Erik
HE
D001093:Arachidonate 15-Lipoxygenase / Q000235:genetics / Q000378:metabolism*; D001095:Arachidonic Acids / Q000378:metabolism; D001249:Asthma / Q000201:enzymology / Q000276:immunology; D005312:Fetal Blood / Q000166:cytology / Q000378:metabolism; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism; D015847:Interleukin-4 / Q000276:immunology*; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D015289:Leukotrienes / Q000378:metabolism; D008054:Lipid Peroxides / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000276:immunology; D008353:Mannitol / Q000378:metabolism; D008407:Mast Cells / Q000166:cytology / Q000201:enzymology* / Q000276:immunology; D012867:Skin / Q000166:cytology / Q000276:immunology; D053802:Tryptases / Q000378:metabolism
D001095:Arachidonic Acids; D006893:Hydroxyeicosatetraenoic Acids; D007527:Isoenzymes; D015289:Leukotrienes; D008054:Lipid Peroxides; D015847:Interleukin-4; D008353:Mannitol; C025086:15-hydroperoxy-5,8,11,13-eicosatetraenoic acid; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid; C054992:15-keto-5,8,11,13-eicosatetraenoic acid; D001093:Arachidonate 15-Lipoxygenase; D053802:Tryptases