Role of leukotriene B4 in the interleukin-4-induced human mononuclear phagocyte activation.
Interleukin-4 (IL-4) induced a time- and dose-dependent production of leukotriene B4 (LTB4) by human resting monocytes indicating that IL-4 induced the activation of the 5-lipoxygenase pathway in resting human monocytes. Maximal effect was observed in the presence of 10 ng/ml IL-4, and in kinetics experiments LTB4 production plateaued 40 min after the onset of stimulation. When stimulated for 48 hr with IL-4, resting human monocytes expressed and released the low-affinity receptor for IgE (CD23) and were partially inhibited in the presence of a highly non-redox 5-lipoxygenase inhibitor (BW B70C), suggesting that the production of LTB4 partially contributed to the IL-4-induced CD23 expression and release. This hypothesis was strengthened by the fact that exogenous LTB4 (10 nM) was found to increase the effect of a suboptimal dose of IL-4 (1 ng/ml). In addition to these phenotypical changes, IL-4 primed the phorbol-12-myristate-13-acetate (PMA)-induced luminol-dependent chemiluminescence response (LDCL) by normal human monocytes, this priming effect being abrogated in the presence of BW B70C. Taken together, these data indicated that IL-4 induced the production of LTB4 by activation of the 5-lipoxygenase pathway in human monocytes, and that the activation of this pathway could upregulate the expression and release of CD23 and the respiratory burst of these cells.
Dugas
N
N
Laboratoire Virus Neurone et Immunité, UFR Kremlin Bicètre, France.
Dugas
B
B
Kolb
J P
JP
Yamaoka
K
K
Delfraiss
J F
JF
Damais
C
C
D018929:Cell Culture Techniques; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D015847:Interleukin-4 / Q000276:immunology*; D007975:Leukotriene B4 / Q000096:biosynthesis / Q000276:immunology*; D008163:Luminescent Measurements; D009000:Monocytes / Q000276:immunology*; D017455:Receptors, IgE / Q000378:metabolism; D011994:Recombinant Proteins / Q000276:immunology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D017455:Receptors, IgE; D011994:Recombinant Proteins; D007975:Leukotriene B4; D015847:Interleukin-4; D013755:Tetradecanoylphorbol Acetate