Identification and characterization of a high-affinity leukotriene B4 receptor on guinea pig T lymphocytes and its regulation by lipoxin A4.
A single class of high affinity leukotriene B4 (LTB4) receptors has been identified on the surface of guinea pig peritoneal exudate T lymphocytes. The Kd of these receptors is 1.6 nM, with a Bmax of 25.2 fmol/10(7) cells (1500 sites/cell). Receptor binding activity can be blocked by specific LTB4 receptor antagonists, but not by a specific LTD4 receptor antagonist, lipoxins A4 or B4 (LXA4, LXB4) or K252a, a protein kinase C inhibitor. Pretreatment of T lymphocytes with phorbol myristyl acetate or LXA4, reduced LTB4 receptor density in a concentration-dependent manner, although similar concentrations of LXB4 had no effect. LTB4 receptor down-modulation by LXA4 was reversed by K252a. 4 alpha-Phorbol 12,13-didecanoate, an inactive structural analogue of phorbol myristyl acetate, did not activate protein kinase C or decrease LTB4 receptor density. These results suggest that LTB4 receptor density on T cells may by ultimately down-regulated by a protein kinase C-dependent mechanism and are consistent with a physiological role of LXA4 in the modulation of inflammatory process.
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Department of Cell Biology, University of Medicine and Dentistry of New Jersey, School of Osteopathic Medicine, Stratford, USA.
Dudhane
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Godfrey
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Wong
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D000818:Animals; D002227:Carbazoles / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology*; D026121:Indole Alkaloids; D007249:Inflammation / Q000209:etiology; D007975:Leukotriene B4 / Q000378:metabolism; D044045:Lipoxins; D011493:Protein Kinase C / Q000502:physiology; D018102:Receptors, Leukotriene B4 / Q000032:analysis / Q000187:drug effects*; D013601:T-Lymphocytes / Q000737:chemistry* / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D002227:Carbazoles; D006893:Hydroxyeicosatetraenoic Acids; D026121:Indole Alkaloids; D044045:Lipoxins; D018102:Receptors, Leukotriene B4; C040527:lipoxin A4; D007975:Leukotriene B4; C049985:staurosporine aglycone; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate