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Platelet-Activating Factor Enhances Interleukin-1 Activity by Alveolar Macrophages : Inhibition by PAF Specific Receptor Antagonists

Lee, Ji-Hee   (Department of Physiology, College of Medicine, Ewha Womans University and Division of Cell Biology, Ewha Medical Research CenterUU0001056  );
  • 초록

    It is becoming increasingly clear that the inflammatory reaction can be ascribed to a complex array of mediators generated and released from activated phagocytes. In this study, the effect of PAF on interleukin-1(IL-1) activity by rat alveolar macrophages(AM) was examined using thymocyte proliferation assay in the supernate of sample obtained after 24 hr culture. When AM were cultured with PAF alone, no change in IL-1 activity was observed. However, the combined addition of PAF and muramyl dipeptide(MDP) or lipopolysaccharide(LPS) to AM cultures markedly enhanced IL-1 activity by 2-3 fold compared with AM cultures with the stimulant alone in a concentration dependent fashion. The peack effect was found at $10^{-8}$ M PAF with MDP and $10^{-14}$ M PAF with LPS. the effect of PAF was also tested in silica, toxic respirable dust, -added AM cultures as well as in the cultures containing bacterial compounds. Although silica did not stimulate the IL-1 activity, PAF could enhance IL-1 activity by 2 fold above the value of the silica-treated AM cultures with the peak response at $10^{-12}$ M PAF. Optimal enhancement of IL-1 activity occured when MDP and PAF were present together at the initiation of the 24 hr AM cultures. Additionaly, the biologically inactive precursor/metabolite of PAF, lyso-PAF failed to induce enhancement of IL-1 activity. When the specific, but structurally different PAF receptor antagonists, BN 52021( $10^{-5}$ M) and CV 3988( $10^{-5}$ M) was treated 15 min before addition of PAF( $10^{-8}$ M) and MDP $(10\;{\mu}g/ml)$ to the AM cultures, it markedly inhibited the enhancement of IL-1 activity induced by PAF. The effects of these PAF antagonists were also observed in LPS $(10\;{\mu}g/ml)$ -stimulated cells. Collectively, these data suggest that PAF enhances IL-1 activity by interaction with a specific receptor.


  • 주제어

    PAF .   IL-1 .   Alveolar macrophages .   PAF antagonists .   Lyso-PAF.  

 저자의 다른 논문

  • Lee, Ji-Hee (6)

    1. 1995 "Effects of In Vitro Exposure to Silica on Bioactive Mediator Release by Alveolar Macrophages" 대한생리학회지 = Korean journal of physiology 29 (1): 1~11    
    2. 1995 "Platelet-Activating Factor Potentiates the Activity of Respiratory Burst and Interleukin-1 in Rat Alveolar Macrophages" 대한생리학회지 = Korean journal of physiology 29 (2): 251~257    
    3. 1996 "Effects of Platelet-Activating Factor on Tumor Necrosis $Factor-_{\alpha}$ Production by Muramyl Dipeptide- or Silica-Stimulated Alveolar Macrophages" 대한생리학회지 = Korean journal of physiology 30 (1): 77~83    
    4. 1998 "Inducible Nitric Oxide Synthase mRNA Expression and Nitric Oxide Production in Silica-Induced Acute Inflammatory Lung Injury" The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology 2 (2): 233~239    
    5. 1998 "Study on the Action by PAF on IL-1 Modulation in Alveolar Macrophages: Involvement of Endogenous Arachidonate Metabolites and Intracellular $Ca^{++}$ Mobilization" The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology 2 (2): 241~249    
    6. 1999 "Acute Pulmonary Responses in Vivo to Silica Complexed with $H^+$, $Zn^{2+}$, or $Fe^{3+}$" The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology 3 (2): 183~189    

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