Neutrophils are immune cells preferentially targeted by retinoic acid in elderly subjects

Abstract

Background: The immune system gradually deteriorates with age and nutritional status is a major factor in immunosenescence. Of the many nutritional factors implicated in age-related immune dysfunction, vitamin A may be a good candidate, since vitamin A concentrations classically decrease during aging whereas it may possess important immunomodulatory properties via its active metabolites, the retinoic acids. This prompted us to investigate the immune response induced by retinoids in adults and elderly healthy subjects. Before and after oral supplementation with 13cis retinoic acid (0.5 mg/kg/day during 28 days), whole blood cells were phenotyped, and functions of peripheral blood mononuclear cells (PBMC) and polymorphonuclear cells (PMN) were investigated by flow cytometry and ELISA tests.

Results: In both young adults (n = 20, 25 ± 4 years) and older subjects (n = 20, 65 ± 4 years), retinoic acid supplementation had no effect on the distribution of leukocyte subpopulations or on the functions of PBMC (Il-2 and sIl-2R production, membrane expression of CD25). Concerning PMN, retinoic acid induced an increase in both spontaneous migration and cell surface expression of CD11b in the two different age populations, whereas bactericidal activity and phagocytosis remained unchanged.

Conclusions: We demonstrated that retinoic acid induces the same intensity of immune response between adult and older subjects, and more specifically affects PMN functions, i.e. adhesion and migration, than PBMC functions.

Figure 1

Neutrophils chemotaxis. Cell migration distances (in mm) are measured microscopically in the direction of the chemoattractant (directed migration (DM)) and towards the control (spontaneous migration (SM)). Neutrophils chemotaxis index is expressed as the ratio of directed to spontaneous migration of PMN cells. x ± SEM; n = 20 subjects per group. Two-way repeated-measures ANOVA was performed to discriminate among the effects of age (A; p < 0.05), nutritional treatment (N; p < 0.05) and their interaction (I; p < 0.05). There was a significant effect of nutritional treatment for both chemotaxis index and spontaneous migration.