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. 1994 Jul;1(4):424–432. doi: 10.1128/cdli.1.4.424-432.1994

Differential effects of interleukin-2 and interleukin-4 on immunomodulatory role of platelet-activating factor in human B cells.

C L Patke 1, C G Green 1, W T Shearer 1
PMCID: PMC368281  PMID: 8556480

Abstract

Platelet-activating factor (PAF), a naturally occurring phospholipid cytokine, is a potent mediator of allergic and inflammatory reactions, as well as a modulator of immune responses. In the present study we showed that PAF is involved in early B-cell activation, as demonstrated by the increased cyclic AMP (cAMP) generation by PAF in a time- and dose-dependent manner in anti-mu antibody- plus B-cell growth factor-activated normal human peripheral blood B lymphocytes. PAF also regulated differentiation by causing a biphasic response on immunoglobulin M (IgM) production with an inhibitory signal generated at 10(-6) M and a stimulatory signal generated at 10(-8) to 10(-10) M. PAF enhanced IgA secretion. The regulation exerted by PAF was shown to be specific because the addition of the PAR antagonist CV-3988 abrogated these effects and the inactive form of PAF, lyso-PAF, induced neither cAMP generation nor immunoglobulin secretion in normal human B cells. Other cytokines, interleukin-2 (IL-2) and IL-4, potent mediators of the immune response, were unable to elicit a cAMP response in B cells. However, the addition of PAF (10(-6) M) with wither IL-2 or IL-4 enhanced cAMP production above the levels enhanced by the addition of PAF alone. IL-2 or IL-4, individually, stimulated IgM production, yet costimulation with PAF resulted in a differential effect between IL-2 and IL-4. PAF down-regulated the IL-4-induced IgM secretion, whereas the IL-2-induced IgM secretion was enhanced. The presence of CV-3988 returned all valued to those obtained with IL-2 or IL-4 alone, demonstrating the specificity of PAF. These data suggest that PAF is an important B-cell immunomodulator which can interact with other leukocyte cell mediators.

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Selected References

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  1. Adolfs M. J., Beusenberg F. D., Bonta I. L. PAF-acether modifies human peritoneal macrophage cAMP levels in a biphasic fashion. Agents Actions. 1989 Jan;26(1-2):119–120. doi: 10.1007/BF02126580. [DOI] [PubMed] [Google Scholar]
  2. Ambrus J. L., Jr, Jurgensen C. H., Bowen D. L., Tomita S., Nakagawa T., Nakagawa N., Goldstein H., Witzel N. L., Mostowski H. S., Fauci A. S. The activation, proliferation, and differentiation of human B lymphocytes. Adv Exp Med Biol. 1987;213:163–175. doi: 10.1007/978-1-4684-5323-2_16. [DOI] [PubMed] [Google Scholar]
  3. Behrens T. W., Goodwin J. S. Control of human T cell proliferation by platelet-activating factor. Int J Immunopharmacol. 1990;12(2):175–184. doi: 10.1016/0192-0561(90)90051-n. [DOI] [PubMed] [Google Scholar]
  4. Brass L. F., Woolkalis M. J., Manning D. R. Interactions in platelets between G proteins and the agonists that stimulate phospholipase C and inhibit adenylyl cyclase. J Biol Chem. 1988 Apr 15;263(11):5348–5355. [PubMed] [Google Scholar]
  5. Burgers J. A., Akkerman J. W. Regulation of the receptor for platelet-activating factor on human platelets. Biochem J. 1993 Apr 1;291(Pt 1):157–161. doi: 10.1042/bj2910157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Callard R. E., Smith S. H., Scott K. E. The role of interleukin 4 in specific antibody responses by human B cells. Int Immunol. 1991 Feb;3(2):157–163. doi: 10.1093/intimm/3.2.157. [DOI] [PubMed] [Google Scholar]
  7. Cambier J. C., Ransom J. T. Molecular mechanisms of transmembrane signaling in B lymphocytes. Annu Rev Immunol. 1987;5:175–199. doi: 10.1146/annurev.iy.05.040187.001135. [DOI] [PubMed] [Google Scholar]
  8. Chao W., Liu H. L., Zhou W. G., Hanahan D. J., Olson M. S. Regulation of platelet-activating factor receptor and platelet-activating factor receptor-mediated biological responses by cAMP in rat Kupffer cells. J Biol Chem. 1990 Oct 15;265(29):17576–17583. [PubMed] [Google Scholar]
  9. Defrance T., Vanbervliet B., Pène J., Banchereau J. Human recombinant IL-4 induces activated B lymphocytes to produce IgG and IgM. J Immunol. 1988 Sep 15;141(6):2000–2005. [PubMed] [Google Scholar]
  10. Deryckx S., de Waal Malefyt R., Gauchat J. F., Vivier E., Thomas Y., de Vries J. E. Immunoregulatory functions of paf-acether. VIII. Inhibition of IL-4-induced human IgE synthesis in vitro. J Immunol. 1992 Mar 1;148(5):1465–1470. [PubMed] [Google Scholar]
  11. Dulioust A., Vivier E., Salem P., Benveniste J., Thomas Y. Immunoregulatory functions of paf-acether. I. Effect of paf-acether on CD4+ cell proliferation. J Immunol. 1988 Jan 1;140(1):240–245. [PubMed] [Google Scholar]
  12. Finney M., Guy G. R., Michell R. H., Gordon J., Dugas B., Rigley K. P., Callard R. E. Interleukin 4 activates human B lymphocytes via transient inositol lipid hydrolysis and delayed cyclic adenosine monophosphate generation. Eur J Immunol. 1990 Jan;20(1):151–156. doi: 10.1002/eji.1830200122. [DOI] [PubMed] [Google Scholar]
  13. Fonteh A. N., Winkler J. D., Torphy T. J., Heravi J., Undem B. J., Chilton F. H. Influence of isoproterenol and phosphodiesterase inhibitors on platelet-activating factor biosynthesis in the human neutrophil. J Immunol. 1993 Jul 1;151(1):339–350. [PubMed] [Google Scholar]
  14. Funderud S., Erikstein B., Asheim H. C., Nustad K., Stokke T., Blomhoff H. K., Holte H., Smeland E. B. Functional properties of CD19+ B lymphocytes positively selected from buffy coats by immunomagnetic separation. Eur J Immunol. 1990 Jan;20(1):201–206. doi: 10.1002/eji.1830200129. [DOI] [PubMed] [Google Scholar]
  15. Galizzi J. P., Cabrillat H., Rousset F., Ménétrier C., de Vries J. E., Banchereau J. IFN-gamma and prostaglandin E2 inhibit IL-4-induced expression of Fc epsilon R2/CD23 on B lymphocytes through different mechanisms without altering binding of IL-4 to its receptor. J Immunol. 1988 Sep 15;141(6):1982–1988. [PubMed] [Google Scholar]
  16. Goldstein H., Koerholz D., Chesky L., Fan X. D., Ambrus J. L., Jr Divergent activities of protein kinases in IL-6-induced differentiation of a human B cell line. J Immunol. 1990 Aug 1;145(3):952–961. [PubMed] [Google Scholar]
  17. Jelinek D. F., Lipsky P. E. Inhibitory influence of IL-4 on human B cell responsiveness. J Immunol. 1988 Jul 1;141(1):164–173. [PubMed] [Google Scholar]
  18. Jelinek D. F., Lipsky P. E. Regulation of human B lymphocyte activation, proliferation, and differentiation. Adv Immunol. 1987;40:1–59. doi: 10.1016/s0065-2776(08)60237-0. [DOI] [PubMed] [Google Scholar]
  19. Kolb J. P., Abadie A., Paul-Eugene N., Dugas B. Intracellular signaling events associated with the induction of DNA synthesis in human B lymphocytes. II. Different pathways triggered by IL-2 and IL-4. Cell Immunol. 1993 Jan;146(1):131–146. doi: 10.1006/cimm.1993.1012. [DOI] [PubMed] [Google Scholar]
  20. Kolb J. P., Tran P. L., Abadie A., Amirand C., Dugas B., Dugas B. Intracellular signaling events associated with the induction of DNA synthesis in human B lymphocytes. I. Stimulation of PKC-dependent and -independent pathways by LMW-BCGF. Cell Immunol. 1993 Jan;146(1):117–130. doi: 10.1006/cimm.1993.1011. [DOI] [PubMed] [Google Scholar]
  21. Kuruvilla A., Putcha G., Poulos E., Shearer W. T. Tyrosine phosphorylation of phospholipase C concomitant with its activation by platelet-activating factor in a human B cell line. J Immunol. 1993 Jul 15;151(2):637–648. [PubMed] [Google Scholar]
  22. Kuruvilla A., Putcha G., Shearer W. T. High-level expression of functional platelet-activating factor receptors on a human B lymphoblastoid cell line. Biochem Biophys Res Commun. 1991 Nov 14;180(3):1318–1324. doi: 10.1016/s0006-291x(05)81339-7. [DOI] [PubMed] [Google Scholar]
  23. Luo H. Y., Hofstetter H., Banchereau J., Delespesse G. Cross-linking of CD23 antigen by its natural ligand (IgE) or by anti-CD23 antibody prevents B lymphocyte proliferation and differentiation. J Immunol. 1991 Apr 1;146(7):2122–2129. [PubMed] [Google Scholar]
  24. Mazer B., Clay K. L., Renz H., Gelfand E. W. Platelet-activating factor enhances Ig production in B lymphoblastoid cell lines. J Immunol. 1990 Oct 15;145(8):2602–2607. [PubMed] [Google Scholar]
  25. Mazer B., Domenico J., Sawami H., Gelfand E. W. Platelet-activating factor induces an increase in intracellular calcium and expression of regulatory genes in human B lymphoblastoid cells. J Immunol. 1991 Mar 15;146(6):1914–1920. [PubMed] [Google Scholar]
  26. Nakanishi K., Hirose S., Yoshimoto T., Ishizashi H., Hiroishi K., Tanaka T., Kono T., Miyasaka M., Taniguchi T., Higashino K. Role and regulation of interleukin (IL)-2 receptor alpha and beta chains in IL-2-driven B-cell growth. Proc Natl Acad Sci U S A. 1992 Apr 15;89(8):3551–3555. doi: 10.1073/pnas.89.8.3551. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Nguer C. M., Pellegrini O., Galanaud P., Benveniste J., Thomas Y., Richard Y. Regulation of paf-acether receptor expression in human B cells. J Immunol. 1992 Oct 15;149(8):2742–2748. [PubMed] [Google Scholar]
  28. O'Flaherty J. T., Redman J. F., Jr, Schmitt J. D., Ellis J. M., Surles J. R., Marx M. H., Piantadosi C., Wykle R. L. 1-O-alkyl-2-N-methylcarbamyl-glycerophosphocholine: a biologically potent, non-metabolizable analog of platelet-activating factor. Biochem Biophys Res Commun. 1987 Aug 31;147(1):18–24. doi: 10.1016/s0006-291x(87)80081-5. [DOI] [PubMed] [Google Scholar]
  29. Patke C. L., Orson F. M., Shearer W. T. Cyclic AMP-mediated modulation of immunoglobulin production in B cells by prostaglandin E1. Cell Immunol. 1991 Oct 1;137(1):36–45. doi: 10.1016/0008-8749(91)90054-f. [DOI] [PubMed] [Google Scholar]
  30. Patke C. L., Shearer W. T. Enhancement of cyclic AMP metabolism in a B cell line by protein kinase C. Cell Immunol. 1990 Oct 1;130(1):22–31. doi: 10.1016/0008-8749(90)90158-n. [DOI] [PubMed] [Google Scholar]
  31. Paul W. E., Mizuguchi J., Brown M., Nakanishi K., Hornbeck P., Rabin E., Ohara J. Regulation of B-lymphocyte activation, proliferation, and immunoglobulin secretion. Cell Immunol. 1986 Apr 15;99(1):7–13. doi: 10.1016/0008-8749(86)90209-1. [DOI] [PubMed] [Google Scholar]
  32. Pène J., Rousset F., Brière F., Chrétien I., Wideman J., Bonnefoy J. Y., De Vries J. E. Interleukin 5 enhances interleukin 4-induced IgE production by normal human B cells. The role of soluble CD23 antigen. Eur J Immunol. 1988 Jun;18(6):929–935. doi: 10.1002/eji.1830180615. [DOI] [PubMed] [Google Scholar]
  33. Raaijmakers J. A., Beneker C., van Geffen E. C., Meisters T. M., Pover P. Inflammatory mediators and beta-adrenoceptor function. Agents Actions. 1989 Jan;26(1-2):45–47. doi: 10.1007/BF02126558. [DOI] [PubMed] [Google Scholar]
  34. Rabin E. M., Mond J. J., Ohara J., Paul W. E. Interferon-gamma inhibits the action of B cell stimulatory factor (BSF)-1 on resting B cells. J Immunol. 1986 Sep 1;137(5):1573–1576. [PubMed] [Google Scholar]
  35. Rasmussen A. M., Smeland E. B., Erikstein B. K., Caignault L., Funderud S. A new method for detachment of Dynabeads from positively selected B lymphocytes. J Immunol Methods. 1992 Feb 5;146(2):195–202. doi: 10.1016/0022-1759(92)90228-l. [DOI] [PubMed] [Google Scholar]
  36. Renz H., Or R., Domenico J., Leung D. Y., Gelfand E. W. Reciprocal regulatory effects of IL-4 on cell growth and immunoglobulin production in Ig-secreting human B-cell lines. Clin Immunol Immunopathol. 1992 Sep;64(3):233–241. doi: 10.1016/0090-1229(92)90205-3. [DOI] [PubMed] [Google Scholar]
  37. Rola-Pleszczynski M., Pouliot C., Turcotte S., Pignol B., Braquet P., Bouvrette L. Immune regulation by platelet-activating factor. I. Induction of suppressor cell activity in human monocytes and CD8+ T cells and of helper cell activity in CD4+ T cells. J Immunol. 1988 May 15;140(10):3547–3552. [PubMed] [Google Scholar]
  38. Rosenblatt H. M., Lewis D. E., Sklar J., Cleary M. L., Parikh N., Galili N., Ritz J., Shearer W. T. Epstein-Barr virus-transformed B-cell line (DV-1) derived from bone marrow of a patient with severe combined immunodeficiency and immunoblastic lymphoma. Pediatr Res. 1987 Apr;21(4):331–337. doi: 10.1203/00006450-198704000-00003. [DOI] [PubMed] [Google Scholar]
  39. Sato T., Bewtra A. K., Hopp R. J., Nair N., Townley R. G. Alpha- and beta-adrenergic-receptor systems in bronchial asthma and in subjects without asthma: reduced mononuclear cell beta-receptors in bronchial asthma. J Allergy Clin Immunol. 1990 Dec;86(6 Pt 1):839–850. doi: 10.1016/s0091-6749(05)80144-7. [DOI] [PubMed] [Google Scholar]
  40. Schulam P. G., Kuruvilla A., Putcha G., Mangus L., Franklin-Johnson J., Shearer W. T. Platelet-activating factor induces phospholipid turnover, calcium flux, arachidonic acid liberation, eicosanoid generation, and oncogene expression in a human B cell line. J Immunol. 1991 Mar 1;146(5):1642–1648. [PubMed] [Google Scholar]
  41. Schulam P. G., Putcha G., Franklin-Johnson J., Shearer W. T. Evidence for a platelet-activating factor receptor on human lymphoblastoid B cells: activation of the phosphatidylinositol cycle and induction of calcium mobilization. Biochem Biophys Res Commun. 1990 Jan 30;166(2):1047–1052. doi: 10.1016/0006-291x(90)90916-b. [DOI] [PubMed] [Google Scholar]
  42. Shearer W. T., Patke C. L., Gilliam E. B., Rosenblatt H. M., Barron K. S., Orson F. M. Modulation of a human lymphoblastoid B cell line by cyclic AMP. Ig secretion and phosphatidylcholine metabolism. J Immunol. 1988 Sep 1;141(5):1678–1686. [PubMed] [Google Scholar]
  43. Snyder F. Biochemistry of platelet-activating factor: a unique class of biologically active phospholipids. Proc Soc Exp Biol Med. 1989 Feb;190(2):125–135. doi: 10.3181/00379727-190-42839. [DOI] [PubMed] [Google Scholar]
  44. Splawski J. B., Jelinek D. F., Lipsky P. E. Immunomodulatory role of IL-4 on the secretion of Ig by human B cells. J Immunol. 1989 Mar 1;142(5):1569–1575. [PubMed] [Google Scholar]
  45. Taieb J., Leca G., Auffredou M. T., Galanaud P., Vazquez A. IL-4 counteracts anti-mu-induced human B cell proliferation: involvement of a cAMP-dependent inhibitory pathway. Eur Cytokine Netw. 1991 Aug-Sep;2(4):265–272. [PubMed] [Google Scholar]
  46. Thivierge M., Alami N., Müller E., de Brum-Fernandes A. J., Rola-Pleszczynski M. Transcriptional modulation of platelet-activating factor receptor gene expression by cyclic AMP. J Biol Chem. 1993 Aug 15;268(23):17457–17462. [PubMed] [Google Scholar]
  47. Tomizawa K., Ishizaka A., Kojima K., Nakanishi M., Sakiyama Y., Matsumoto S. Interleukin-4 regulates the interleukin-2 receptors on human peripheral blood B lymphocytes. Clin Exp Immunol. 1991 Mar;83(3):492–496. doi: 10.1111/j.1365-2249.1991.tb05667.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Vazquez A., Auffredou M. T., Chaouchi N., Taieb J., Sharma S., Galanaud P., Leca G. Differential inhibition of interleukin 2- and interleukin 4-mediated human B cell proliferation by ionomycin: a possible regulatory role for apoptosis. Eur J Immunol. 1991 Oct;21(10):2311–2316. doi: 10.1002/eji.1830211004. [DOI] [PubMed] [Google Scholar]
  49. Vazquez A., Auffredou M. T., Galanaud P., Leca G. Modulation of IL-2- and IL-4-dependent human B cell proliferation by cyclic AMP. J Immunol. 1991 Jun 15;146(12):4222–4227. [PubMed] [Google Scholar]
  50. Ventura M. A., Ribier A., Delbourg I., Chambaut-Guerin A. M., Thomopoulos P. The adhesiveness of monocytic U937 cells is stimulated by pro-inflammatory agents and inhibited by adenosine 3':5'-cyclic monophosphate. Biochem Pharmacol. 1990 Feb 15;39(4):677–683. doi: 10.1016/0006-2952(90)90145-b. [DOI] [PubMed] [Google Scholar]
  51. Wang S., Townley R. G. Effects of platelet activating factor on cyclic AMP accumulation in human lymphocytes. Ann Allergy. 1992 Aug;69(2):140–142. [PubMed] [Google Scholar]

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