Dose-dependent agonist and antagonist effects of the platelet-activating factor analogue 1-palmitoyl-2-acetoyl-sn-glycero-3-phosphocholine on B lymphocytes

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Presentation transcript:

Dose-dependent agonist and antagonist effects of the platelet-activating factor analogue 1-palmitoyl-2-acetoyl-sn-glycero-3-phosphocholine on B lymphocytes Bruce D. Mazer, MD, Baruch Toledano, MD, Mehrdad Saririan, MD, Yolande Bastien, BSc Journal of Allergy and Clinical Immunology Volume 102, Issue 2, Pages 231-237 (August 1998) DOI: 10.1016/S0091-6749(98)70091-0 Copyright © 1998 Mosby, Inc. Terms and Conditions

Fig. 1 PAF and PAGPC increase IgM secretion in Ramos cells. Ramos cells (3.5 × 105) were cultured for 72 hours with doses of PAF (A) or PAGPC (B) as indicated. Both lipid mediators increased secretion of IgM by Ramos cells in a dose-dependent fashion. Baseline IgM levels ranged from 120 to 360 ng/mL. n = 6. *P ≤ .05. Journal of Allergy and Clinical Immunology 1998 102, 231-237DOI: (10.1016/S0091-6749(98)70091-0) Copyright © 1998 Mosby, Inc. Terms and Conditions

Fig. 2 Comparison of the effects of high- and low-dose PAGPC on the PAF receptor. Ramos cells were incubated with PAF (10–7 mol/l), PAGPC (h) (10–6 mol/l), PAGPC (l) (10–12 mol/l), and/or the PAF antagonist Web 2170 (10–6 mol/l). A indicates that Web 2170 inhibits both the effect of PAF 10–9 mol/l and PAGPC (h). B, PAGPC (l) acts as a PAF receptor antagonist, inhibiting the PAF-induced increase of IgM as effectively as Web 2170. n = 4. *P ≤ .05. Journal of Allergy and Clinical Immunology 1998 102, 231-237DOI: (10.1016/S0091-6749(98)70091-0) Copyright © 1998 Mosby, Inc. Terms and Conditions

Fig. 3 PAGPC inhibits the ability of PAF to rescue Ramos cells from programmed cell death. Ramos cells were incubated with αIgM (2 μg/mL) and/or PAF 10–7 mol/L; indicated cultures were preincubated with PAGPC (l) (10–12 mol/L) or Web 2170 (10–6 mol/L) for 10 minutes. After 24 hours, cell viability was assessed by flow cytometry after propidium iodide staining. PAF rescues cells from αIgM-induced apoptosis. This is inhibited by both PAGPC (l) and Web 2170. n = 3; *P ≤ .05. Journal of Allergy and Clinical Immunology 1998 102, 231-237DOI: (10.1016/S0091-6749(98)70091-0) Copyright © 1998 Mosby, Inc. Terms and Conditions

Fig. 4 Low concentrations of PAGPC inhibits the ability of PAF to rescue Ramos cells from the effects of αIgM ligation. A, αIgM (2 μg/mL) inhibits the constitutive secretion of IgM antibodies by Ramos cells. Coincubation of Ramos cells with αIgM and PAF (10–7 mol/L) restores normal IgM secretion. Both PAGPC (l) (10–12 mol/L) and Web 2170 inhibit the action of PAF. B, Ramos cells were incubated with vehicle (0), PAGPC (l) (10–12 mol/L), or Web 2170 for 10 minutes, then washed extensively with PBS plus 1% BSA [signified by (:)]. BSA washing does not reverse the antagonistic effect of PAGPC, suggesting homologous desensitization of the PAF receptor. Both panels, n = 3; *P ≤ .05. Journal of Allergy and Clinical Immunology 1998 102, 231-237DOI: (10.1016/S0091-6749(98)70091-0) Copyright © 1998 Mosby, Inc. Terms and Conditions