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The lactoferrin receptor may mediate the reduction of eosinophils in the duodenum of pigs consuming milk containing recombinant human lactoferrin

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Abstract

Lactoferrin is part of the immune system and multiple tissues including the gastrointestinal (GI) tract, liver, and lung contain receptors for lactoferrin. Lactoferrin has many functions, including antimicrobial, immunomodulatory, and iron binding. Additionally, lactoferrin inhibits the migration of eosinophils, which are constitutively present in the GI tract, and increase during inflammation. Lactoferrin suppresses eosinophil infiltration into the lungs and eosinophil migration in -vitro. Healthy pigs have a large population of eosinophils in their small intestine and like humans, pigs have small intestinal lactoferrin receptors (LFR); thus, pigs were chosen to investigate the effects of consumption of milk containing recombinant human lactoferrin (rhLF-milk) on small intestinal eosinophils and expression of eosinophilic cytokines. In addition, LFR localization was analyzed in duodenum and circulating eosinophils to determine if the LFR could play a role in lactoferrin’s ability to inhibit eosinophil migration. In the duodenum there were significantly fewer eosinophils/unit area in pigs fed rhLF-milk compared to pigs fed control milk (p = 0.025); this was not seen in the ileum (p = 0.669). In the duodenum, no differences were observed in expression of the LFR, or any eosinophil migratory cytokines, and the amount of LFR protein was not different (p = 0.386). Immunohistochemistry (IHC) showed that within the duodenum the LFR localized on the brush border of villi, crypts, and within the lamina propria. Circulating eosinophils also contained LFRs, which may be a mechanism allowing lactoferrin to directly inhibit eosinophil migration.

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Acknowledgments

We would like to thank Pharming Group NV for providing the recombinant human lactoferrin milk and Doug Gisi and the UC-Davis Dairy Barn staff for providing control milk. We also thank Kent Parker and the UC-Davis Swine facility staff for assistance with pig rearing. We thank Danielle and Miranda George for help examining the histological slides, Samantha Lotti for help processing intestinal samples for qRT-PCR, Dr.Barbara Nitta-Oda for assistance with immunohistochemistry and immunocytochemistry, and Sean Owens (DVM) for his insight into porcine histopathology. This work was supported by a Jastro-Shields grant from the University of California, Davis.

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The authors declare no conflict of interest.

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Authors and Affiliations

  1. Department of Animal Science, University of California, Davis, CA, USA

    Caitlin Cooper & James Murray

  2. Department of Nutrition, University of California, Davis, CA, USA

    Eric Nonnecke & Bo Lönnerdal

  3. Departments of Internal Medicine, University of California, Davis, CA, USA

    Bo Lönnerdal

  4. Department of Population Health and Reproduction, University of California, One Shields Ave, Davis, CA, 95616, USA

    James Murray

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  1. Caitlin Cooper
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  2. Eric Nonnecke
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  3. Bo Lönnerdal
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  4. James Murray
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Correspondence to Caitlin Cooper.

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Cooper, C., Nonnecke, E., Lönnerdal, B. et al. The lactoferrin receptor may mediate the reduction of eosinophils in the duodenum of pigs consuming milk containing recombinant human lactoferrin. Biometals 27, 1031–1038 (2014). https://doi.org/10.1007/s10534-014-9778-8

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  • DOI: https://doi.org/10.1007/s10534-014-9778-8

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