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Folate receptor expression on murine and human adipose tissue macrophages

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Abstract

Objective and design

Adipose tissue macrophages (ATMs) have been implicated in a number of obesity-related diseases. Because the activated macrophages associated with many types of autoimmune and inflammatory diseases express a folate receptor (FR) that can be exploited for FR-targeted drug delivery, we examined the visceral adipose tissue of obese mice and humans to determine whether ATMs also express FR that are accessible by folate conjugates.

Material or subjects

C57BL/6 or FATSO mice fed on either a low- or high-fat diet were used in murine studies. Human adipose tissue were obtained from healthy volunteers during adipose reduction surgery.

Methods

Visceral adipose tissue was collected from both obese mice and humans, collagenase digested, and stained with folate-Oregon Green and antibodies for macrophage markers including F4/80, mannose receptor (CD206), CD11b, and CD11c. Cells were then examined for expression of the above markers by flow cytometry. Furthermore, the ability of folate conjugates to target the FR-expressing ATMs in obese mice was evaluated in vivo.

Results

A subset of the ATMs harvested from obese mice were found to express FR. Subpopulations of ATMs also simultaneously express both pro- and anti-inflammatory markers, and FR is expressed on both subsets. We then demonstrate that FR-expressing ATMs can be targeted with folate-linked fluorescent dyes in vivo.

Conclusions

FR are expressed on multiple subsets of ATMs and these subsets can be targeted with folate-linked drugs, allowing for the possible development of FR-targeted therapies for obesity-related inflammatory diseases.

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Acknowledgments

We thank Endocyte Inc. (West Lafayette, IN) for generous financial support, for the gift of folate-targeted 99mTc (EC20), folate-FITC (EC17), folate-Oregon Green, and folate-Alexa Fluor 647 used in the experiments, and helpful conversations regarding experimental design. We are extremely grateful to the physicians at Baldwin Plastic Surgery Center, Lafayette, IN for providing the human adipose tissue samples analyzed in the reported studies. Furthermore, we thank Dr. Chris V. Galliford for his help with preparing this manuscript for publication.

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Authors and Affiliations

  1. Department of Chemistry, Purdue University, 720 Clinic Drive, West Lafayette, IN, 47907-2084, USA

    Michael J. Hansen, N. Achini Bandara & Philip S. Low

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  1. Michael J. Hansen
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  2. N. Achini Bandara
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  3. Philip S. Low
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Correspondence to Philip S. Low.

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Responsible Editor: Bernhard Gibbs.

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Hansen, M.J., Achini Bandara, N. & Low, P.S. Folate receptor expression on murine and human adipose tissue macrophages. Inflamm. Res. 64, 697–706 (2015). https://doi.org/10.1007/s00011-015-0849-2

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  • DOI: https://doi.org/10.1007/s00011-015-0849-2

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