Lactodifucotetraose, a human milk oligosaccharide, attenuates platelet function and inflammatory cytokine release

Abstract

Human milk strongly quenches inflammatory processes in vitro, and breastfed infants have lower incidence of inflammatory diseases than those fed artificially. Platelets from neonates, in contrast to those from adults, are less responsive to platelet agonists such as collagen, thrombin, ADP, and epinephrine. Breastfed infants absorb oligosaccharides intact from the human milk in their gut to the circulation. This study was to determine whether these oligosaccharides can attenuate platelet function and platelet secretion of pro-inflammatory proteins, and to identify the active component. The natural mixture of oligosaccharides from human milk and pure individual human milk oligosaccharides were tested for their ability to modulate responses of platelets isolated from human blood following exposure to thrombin, ADP, and collagen. Human milk and the natural mixture of human milk oligosaccharides inhibited platelet release of inflammatory proteins. Of the purified human milk oligosaccharides tested, only lactodifucotetraose (LDFT) significantly inhibited thrombin induced release of the pro-inflammatory proteins RANTES and sCD40L. LDFT also inhibited platelet adhesion to a collagen-coated surface, as well as platelet aggregation induced by ADP or collagen. These data indicate that LDFT may help modulate hemostasis by suppressing platelet-induced inflammatory processes in breastfed infants. This activity suggests further study of LDFT for its potential as a therapeutic agent in infants and adults.

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Acknowledgments

Supported in part by the National Institute of Allergy and Infectious Diseases AI075563, Eunice Kennedy Shriver National Institute of Child Health and Human Development HD013021 and HD059140. The authors appreciate the assistance of Dr. N. Nanda Nanthakumar in the design of the figures.

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Correspondence to David S. Newburg.

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DSN owns stock in Glycosyn, LLC, which makes human milk oligosaccharides. This competition of interests is being managed by Boston College. The other authors have no competing interests to disclose.

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Newburg, D.S., Tanritanir, A.C. & Chakrabarti, S. Lactodifucotetraose, a human milk oligosaccharide, attenuates platelet function and inflammatory cytokine release. J Thromb Thrombolysis 42, 46–55 (2016). https://doi.org/10.1007/s11239-015-1331-2

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Keywords

  • Human milk oligosaccharides
  • Lactodifucotetraose
  • Platelets
  • Inflammation
  • RANTES
  • Aggregation