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Differential-effects of 20-trifluoromethyl leukotriene-b4 on human neutrophil functions

Academic Article
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Overview

authors

  • Tsai, B. S.
  • Keith, R. H.
  • Villaniprice, D.
  • Haack, R. A.
  • Bauer, R. F.
  • Leonard, R.
  • Abe, Y.
  • Nicolaou, K.C.

publication date

  • February 1989

journal

  • Prostaglandins  Journal

abstract

  • A leukotriene B4 (LTB4) analog, 20-trifluoromethyl LTB4 (20CF3-LTB4), has been synthesized and evaluated with human neutrophils for effects on chemotaxis and degranulation. 20CF3-LTB4 was equipotent to LTB4 as a chemoattractant (EC50, 3 nM), produced 50% of maximal activity of LTB4, and competed with [H] LTB4 for binding to intact human neutrophil LTB4 receptors. In contrast to chemotactic activity, 20CF3-LTB4 in nanomolar concentrations exhibited antagonist activity without agonist activity up to 10 microM on LTB4-induced degranulation. The analog had no significant effect on degranulation induced by the chemoattractant peptide, N-formyl-methionyl-leucyl-phenylalanine (fMLP). Like LTB4, 20CF3-LTB4 induced neutrophil desensitization to degranulation by LTB4. The results indicate that hydrogen atoms at C-20 of LTB4 are critical for its intrinsic chemotactic and degranulation activities. The fact that 20CF3-LTB4 is a partial agonist for chemotaxis and an antagonist for degranulation suggests that different LTB4 receptor subtypes are coupled to these neutrophil functions. Desensitization of the neutrophil degranulation response to LTB4 can result from receptor occupancy by an antagonist, and therefore, the desensitization is not specific for an agonist.

subject areas

  • Binding, Competitive
  • Chemotaxis, Leukocyte
  • Cytoplasmic Granules
  • Humans
  • In Vitro Techniques
  • Leukotriene B4
  • Neutrophils
  • Peroxidase
  • Receptors, Immunologic
  • Receptors, Leukotriene B4
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Identity

International Standard Serial Number (ISSN)

  • 0090-6980

Digital Object Identifier (DOI)

  • 10.1016/0090-6980(89)90064-6

PubMed ID

  • 2543037
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Additional Document Info

start page

  • 287

end page

  • 302

volume

  • 37

issue

  • 2

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