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13C-lutein is differentially distributed in tissues of an adult female rhesus macaque following a single oral administration: a pilot study.

ABSTRACT: Despite the growing awareness regarding lutein's putative roles in eyes and brain, its pharmacokinetics and tissue distribution in primates have been poorly understood. We hypothesized that 13C-lutein will be differentially distributed into tissues of an adult rhesus macaque (Macaca mulatta) 3 days following a single oral dose. After a year of prefeeding a diet supplemented with unlabeled lutein (1??mol/kg/d), a 19-year-old female was dosed with 1.92?mg of highly enriched 13C-lutein. Tissues of a nondosed, lutein-fed monkey were used as a reference for natural abundance of 13C-lutein. On the third day postdose, plasma and multiple tissues were collected. Lutein was quantified by high-performance liquid chromatography-photodiode array detector, and 13C-lutein tissue enrichment was determined by liquid chromatography quadrupole time-of-flight mass spectrometry. In the tissues of a reference monkey, 12C-lutein with natural abundance of 13C-lutein was detectable. In the dosed monkey, highly enriched 13C-lutein was observed in all analyzed tissues except for the macular and peripheral retina, with the highest concentrations in the liver followed by the adrenal gland and plasma. 13C-lutein accumulated differentially across 6 brain regions. In adipose depots, 13C-lutein was observed, with the highest concentrations in the axillary brown adipose tissues. In summary, we evaluated 13C-lutein tissue distribution in a nonhuman primate following a single dose of isotopically labeled lutein. These results show that tissue distribution 3?days following a dose of lutein varied substantially dependent on tissue type.

SUBMITTER: Jeon S

PROVIDER: S-EPMC6348040 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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13C-lutein is differentially distributed in tissues of an adult female rhesus macaque following a single oral administration: a pilot study.

Jeon Sookyoung S Li Qiyao Q Rubakhin Stanislav S SS Sweedler Jonathan V JV Smith Joshua W JW Neuringer Martha M Kuchan Matthew M Erdman John W JW

Nutrition research (New York, N.Y.) 20181028

Despite the growing awareness regarding lutein's putative roles in eyes and brain, its pharmacokinetics and tissue distribution in primates have been poorly understood. We hypothesized that 13C-lutein will be differentially distributed into tissues of an adult rhesus macaque (Macaca mulatta) 3 days following a single oral dose. After a year of prefeeding a diet supplemented with unlabeled lutein (1 μmol/kg/d), a 19-year-old female was dosed with 1.92 mg of highly enriched 13</sup ...[more]

PMID: 30522845

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Project description:CD49a+ tissue resident NK cells have been implicated in memory-like NK cell responses, but while this population is well-characterized in mice and in humans, they are poorly described in non-human primates (NHP) which are particularly critical for modeling human viral infections. Others and we have shown that memory-like NK cells are enriched in the liver and because of the importance of NHP in modeling HIV infection, understanding the immunobiology of CD49a+ NK cells in SIV-infected rhesus macaques is critical to explore the role of this cell type in retroviral infections. In this study mononuclear cells isolated from livers, spleens, and peripheral whole blood were analyzed in acutely and chronically lentivirus-infected and experimentally-naïve Indian rhesus macaques (RM). NK cells were then identified as CD45+CD14-CD20-CD3-NKG2A/C+ cells and characterized using multiparametric flow-cytometry. Our data show that in RM, CD49a+ NK cells increase in the liver following retroviral infections [median = 5.2% (naïve) vs. median = 9.48% (SIV+) or median = 16.8% (SHIV+)]. In contrast, there is little change in CD49a+ NK frequencies in whole blood or spleens of matched animals. In agreement with human and murine data we also observed that CD49a+ NK cells were predominantly Eomeslow T-betlow, though these frequencies are elevated in infected animal cohorts. Functionally, our data suggests that infection alters TNF-α, IFN-γ, and CD107a expression in stimulated CD49a+ NK cells. Specifically, our analyses found a decrease in CD49a+ CD107a+ TNFα+ IFNγ- NK cells, with a simultaneous increase in CD49a+ CD107a+ TNFα- IFNγ+ NK cells and the non-responsive CD49a+ CD107a- TNFα- IFNγ- NK cell population following infection, suggesting both pathogenic and inflammatory changes in the NK cell functional profile. Our data also identified significant global differences in polyfunctionality between CD49a+ NK cells in the naïve and chronic (SHIV+) cohorts. Our work provides the first characterization of CD49a+ NK cells in tissues from RM. The significant similarities between CD49a+ NK cells from RM and what is reported from human samples justifies the importance of studying CD49a+ NK cells in this species to support preclinical animal model research.

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Dataset Information

13C-lutein is differentially distributed in tissues of an adult female rhesus macaque following a single oral administration: a pilot study.

Publications

<sup>13</sup>C-lutein is differentially distributed in tissues of an adult female rhesus macaque following a single oral administration: a pilot study.

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