Phosphatidylserine counteracts physiological and pharmacological suppression of humoral immune response.
Phosphatidylserine (PS) is a necessary cofactor for protein kinase C (PKC) activation, and changes in the synthesis of PS have been shown to participate in the mechanism(s) involved in the transmembrane signaling of interleukin 1 (IL-1). In view of the age-associated defects in T-cell functions, in the present study we have addressed the question of whether an in vivo treatment with PS might interfere with such processes. Furthermore, the effect of an in vitro treatment with PS in human peripheral blood monocytes (PBMC) or splenocytes activated with a lectin mitogen, on the expression of IL-2 receptor, was assessed. While the process of ageing was accompanied by a marked decline of humoral response monitored by anti-BSA antibodies (of the IgG class) production, following immunization with BSA in complete Freund adjuvant, chronic treatment with PS (50 mg/kg, in drinking water), reversed this effect, raising specific antibody titers to levels practically indistinguishable from those measured in young animals. Pharmacological depression of humoral immune response induced by a treatment of adult animals with dexamethasone was similarly reversed by a chronic treatment with PS. While only a pharmacological concentration (10(-5) M) of PS significantly increased IL-2 receptor expression in activated human PBMC, simultaneous treatment of PBMC with inactive doses of PS and the pharmacological activator of PKC (phorbol myristate acetate, PMA, 10(-8) M) resulted in a synergistic stimulation of Tac+ cells. Furthermore, in cultures of rat splenocytes PS (10(-6) M) significantly stimulated the expression of IL-2 receptor, and concomitant addition of PS (10(-7) M) to Con A-stimulated splenocytes produced a significant potentiation of IL-2 receptor induction. The present results indicate that in vivo treatment of ageing animals with the specific phospholipid PS is able to reverse the physiological decline of the humoral immune response induced by the ageing process. Moreover, treatment of young rats with PS reversed the pharmacological associated depression of specific antibody production. The in vitro effects of the phospholipid on human PBMC and rat splenocytes might suggest that PS is implicated in T-cell activation through its action on IL-2 receptor.
Department of Pharmacology, Medical School, University of Catania, Italy.
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Guarcello
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Triolo
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Cioni
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Morale
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Farinella
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Scapagnini
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Marchetti
D000375:Aging / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D000818:Animals; D005260:Female; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D010718:Phosphatidylserines / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D015375:Receptors, Interleukin-2 / Q000187:drug effects / Q000378:metabolism; D013154:Spleen / Q000187:drug effects / Q000276:immunology
D010718:Phosphatidylserines; D015375:Receptors, Interleukin-2; D011493:Protein Kinase C