Immunoregulatory activity of the natural product laminarin varies widely as a result lt of its physical properties1

• Published in: The Journal of immunology (1950) 2017-12, Vol.200 (2), p.788-799
• Main Authors: Smith, Alyson J., Graves, Bridget, Child, Robert, Rice, Peter J., Ma, Zuchao, Lowman, Douglas W., Ensley, Harry E., Ryter, Kendal T., Evans, Jay T., Williams, David L.
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1701258

Ligation of Dectin-1 by fungal glucans elicits a Th17 response that is necessary for clearing many fungal pathogens. Laminarin is a (1→3, 1→6)-β glucan that is widely reported to be a Dectin-1 antagonist, however, there are reports that laminarin is also a Dectin-1 agonist. To address this controversy, we assessed the physical properties, structure, purity, Dectin-1 binding and biological activity of five different laminarin preparations from three different commercial sources. 1H-NMR analysis indicated that all of the preparations contained laminarin though their molecular weight varied considerably (4400 to 34400 D). Two of the laminarins contained substantial quantities of very low Mw compounds, some of which were not laminarin. These low Mw moieties could be significantly reduced by extensive dialysis. All of the laminarin preparations were bound by recombinant hDectin-1 and mDectin-1, but the affinity varied considerably and binding affinity did not correlate with Dectin-1 agonism, antagonism or potency. In both human and mouse cells, two laminarins were Dectin-1 antagonists and two were Dectin-1 agonists. The remaining laminarin was a Dectin-1 antagonist, but when the low Mw moieties were removed it became an agonist. We were able to identify a laminarin which is a Dectin-1 agonist and a laminarin that is Dectin-1 antagonist, both of which are relatively pure preparations. These laminarins may be useful in elucidating the structure/activity relationships of glucan/Dectin-1 interactions. Our data demonstrate that laminarin can be either a Dectin-1 antagonist or agonist, depending on the physicochemical properties, purity and structure of the laminarin preparation employed.