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Development and application of monoclonal antibodies in studies of the human leukotriene B4 receptor, BLT1

Pettersson, Annika LU (2005)
Abstract
Infection and inflammation are characterized by the release of chemotactic substances that activate cells of the immune system. One of these important mediators is LTB4, an arachidonic acid derivate that attracts e.g. monocytes and granulocytes to inflammatory sites and induces phagocytosis and degranulation. LTB4 binds to BLT1 which is a 7-transmembrane receptor that belongs to the superfamily of G protein-coupled receptors (GPCRs). BLT1 and LTB4 are not only important in physiological processes but also in several pathological conditions such as psoriasis, arthritis and atherosclerosis.



Monoclonal antibodies recognizing BLT1 were developed using the hybridoma technique and they were extensively characterized with... (More)
Infection and inflammation are characterized by the release of chemotactic substances that activate cells of the immune system. One of these important mediators is LTB4, an arachidonic acid derivate that attracts e.g. monocytes and granulocytes to inflammatory sites and induces phagocytosis and degranulation. LTB4 binds to BLT1 which is a 7-transmembrane receptor that belongs to the superfamily of G protein-coupled receptors (GPCRs). BLT1 and LTB4 are not only important in physiological processes but also in several pathological conditions such as psoriasis, arthritis and atherosclerosis.



Monoclonal antibodies recognizing BLT1 were developed using the hybridoma technique and they were extensively characterized with regard to specificity and applicability. The resulting two antibodies were then applied in a flow cytometric mapping of human peripheral blood and bone marrow where the highest expression of BLT1 was seen in myeloid cells.



One of the antibodies was found to inhibit LTB4 binding to BLT1 while both antibodies could inhibit receptor activation and chemotaxis towards LTB4. These findings demonstrated that one antibody was a competitive antagonist, and the other a non-competitive antagonist.



Myeloid expression of BLT1 was further investigated in monocytes using real-time PCR and flow cytomtery. Pro- and anti-inflammatory mediators were shown to modulate both mRNA and protein levels. A closer analysis of IFN-g-mediated effects was conducted and this mediator down-modulated BLT1 mRNA in a time and concentration dependent manner as well as inhibited LTB4 mediated chemotaxis. (Less)
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author
supervisor
opponent
  • Professor Claesson, Hans-Erik, Karolinska Institutet, Stockholm
organization
publishing date
type
Thesis
publication status
published
subject
keywords
serologi, transplantation, Immunologi, Immunology, serology, antibodies, BLT1, LTB4
pages
110 pages
publisher
Department of Physiological Sciences, Lund University
defense location
Segerfalksalen, WNC, Lund
defense date
2005-04-22 09:00:00
ISBN
91-85439-19-3
language
English
LU publication?
yes
additional info
Annika Pettersson, Åke Boketoft, Alan Sabirsh, Niclas E. Nilsson, Knut Kotarsky, Björn Olde and Christer Owman. 2000. First-Generation Monoclonal Antibodies Identifying the Human Leukotriene B4 Receptor-1 Biochemical and Biophysical Research Communications, vol 279 pp 520-525. Academic Press
Annika Pettersson, Johan Richter and Christer Owman. 2003. Flow cytometric mapping of the leukotriene B4 receptor, BLT1, in human bone marrow and peripheral blood using specific monoclonal antibodies International Immunopharmacology, vol 3 pp 1467-1475. Elsevier
Alan Sabirsh, Annika Pettersson, Åke Boketoft, Knut Kotarsky and Christer Owman. 2003. Differential inhibition of receptor activation by two mouse monoclonal antibodies specific for the human leukotriene B4 receptor, BLT1 International Immunopharmacology, vol 3 pp 1829-1839. Elsevier
Annika Pettersson, Alan Sabirsh, Jesper Bristulf, Karin Kidd-Ljunggren, Bengt Ljungberg, Christer Owman and Ulf Karlsson. 2005. Pro- and anti-inflammatory substances modulate expression of the leukotriene B4 receptor, BLT1, in human monocytes Journal of leukocyte biology, vol 77 The society for Leukocyte Biology (inpress)
id
6303429f-2ff2-4b0a-ac86-bf822b713435 (old id 544584)
date added to LUP
2016-04-01 16:12:53
date last changed
2018-11-21 20:39:38
@phdthesis{6303429f-2ff2-4b0a-ac86-bf822b713435,
  abstract     = {{Infection and inflammation are characterized by the release of chemotactic substances that activate cells of the immune system. One of these important mediators is LTB4, an arachidonic acid derivate that attracts e.g. monocytes and granulocytes to inflammatory sites and induces phagocytosis and degranulation. LTB4 binds to BLT1 which is a 7-transmembrane receptor that belongs to the superfamily of G protein-coupled receptors (GPCRs). BLT1 and LTB4 are not only important in physiological processes but also in several pathological conditions such as psoriasis, arthritis and atherosclerosis.<br/><br>
<br/><br>
Monoclonal antibodies recognizing BLT1 were developed using the hybridoma technique and they were extensively characterized with regard to specificity and applicability. The resulting two antibodies were then applied in a flow cytometric mapping of human peripheral blood and bone marrow where the highest expression of BLT1 was seen in myeloid cells.<br/><br>
<br/><br>
One of the antibodies was found to inhibit LTB4 binding to BLT1 while both antibodies could inhibit receptor activation and chemotaxis towards LTB4. These findings demonstrated that one antibody was a competitive antagonist, and the other a non-competitive antagonist.<br/><br>
<br/><br>
Myeloid expression of BLT1 was further investigated in monocytes using real-time PCR and flow cytomtery. Pro- and anti-inflammatory mediators were shown to modulate both mRNA and protein levels. A closer analysis of IFN-g-mediated effects was conducted and this mediator down-modulated BLT1 mRNA in a time and concentration dependent manner as well as inhibited LTB4 mediated chemotaxis.}},
  author       = {{Pettersson, Annika}},
  isbn         = {{91-85439-19-3}},
  keywords     = {{serologi; transplantation; Immunologi; Immunology; serology; antibodies; BLT1; LTB4}},
  language     = {{eng}},
  publisher    = {{Department of Physiological Sciences, Lund University}},
  school       = {{Lund University}},
  title        = {{Development and application of monoclonal antibodies in studies of the human leukotriene B4 receptor, BLT1}},
  year         = {{2005}},
}