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.
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
Magdalena
M
Gulliksson
Asa
A
Brunnström
Malin
M
Johannesson
Linda
L
Backman
Gunnar
G
Nilsson
Ilkka
I
Harvima
Barbro
B
Dahlén
Maria
M
Kumlin
Hans-Erik
HE
Claesson
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