NEW INSIGHTS IN THE POTENTIAL

NEW INSIGHTS IN THE POTENTIAL

MECHANISM OF ACTION OF NUCLEOTIDES TO MODULATE IMMUNITY

M. Manzano

, A. Gil

, R. Rueda

1

International R&D, Ross Products División, Abbott Laboratories, Granada, Spain,

2

B

2

iochemistry and Molecular Biology Department, University of Granada, Granada, Spain

Introduction: Different immunological functions have been reported to be modulated by nucleotides, but most of these reports suggest that nucleotides exert the greatest impact on the immune system by modulating immunoglobulin production. This in turn may have a clinical relevance for the neonate preventing the incidence and duration of episodes of diarrhoea and infections.

Our group has previously reported that dietary nucleotides modulate positively the production of IgA, but also of IgM. The main goal of this work is to describe a potential mechanism of action to explain how dietary nucleotides modulate immunoglobulin production.

Methods: The influence of dietary nucleotides on the expression of surface antigens characteristic of different intestinal lymphocyte subpopulations, on the expression of B-1 cell antigens by peritoneal cells, which constitutes the main reservoir of B-1 cells, and on the production of IL-2 and IFN- γ (Type 1 γ cytokines) and of IL-5 and IL-6 (Type 2 cytokines) by Peyer’s patch lymphocytes, investigated through flow cytometry in mice at weaning.

Results: Dietary nucleotides significantly increased the percentage of Peyer’s patch lymphocytes expressing CD22 (a B cell marker), and increased the percentage of lamina propria and peritoneal lymphocytes expressing CD5. CD5 is expressed by B-1 cells that are precursors of IgA-producing intestinal plasma cells and of IgM and IgA-producing plasma cells in peripheral blood. Moreover, a dietary nucleotides modified the Peyer’s patch lymphocyte production of Type 1 and Type 2 cytokines, that are involved in the differentiation of intestinal B cells to plasma cells that synthesize and secrete IgA. These results suggest that dietary nucleotides promote intestinal lymphocyte maturation, modulating the production of Type 1 (IL-2) and Type 2 (IL-6) cytokines that are involved in the differentiation of intestinal B cells to plasma cells synthesizing and secreting IgA. Moreover, nucleotides modulate positively the maturation and differentiation of B-1 cells.

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ACTION OF NUCLEOTIDES TO MODULATE IMUNITY 173 Conclusion: All these data might explain how dietary nucleotides modulating the regional immunity can also modulate the systemic immunity and also substantiate the hypothesis that the mechanism by which nucleotides affect immune function is more likely to be a receptor-mediated event than simply being a raw material for nucleic acid replication.

Keywords: dietary nucleotides, B-1 cells, immunoglobulins, cytokines.