Soluble glucan is internalized and trafficked to the Golgi apparatus in macrophages via a clathrin-mediated, lipid raft-regulated mechanism.
Glucans are natural product carbohydrates that stimulate immunity. Glucans are internalized by the pattern recognition receptor, Dectin-1. Glucans were thought to be trafficked to phagolysosomes, but this is unproven. We examined the internalization and trafficking of soluble glucans in macrophages. Incubation of macrophages with glucan resulted in internalization of Dectin-1 and glucan. Inhibition of clathrin blocked internalization of the Dectin-1/glucan complex. Lipid raft depletion resulted in decreased Dectin levels and glucan uptake. Once internalized, glucans colocalized with early endosomes at 0 to 15 min, with the Golgi apparatus at 15 min to 24 h, and with Dectin-1 immediately (0 h) and again later (15 min-24 h). Glucans did not colocalize with lysosomes at any time interval examined. We conclude that the internalization of Dectin-1/glucan complexes in macrophages is mediated by clathrin and negatively regulated by lipid rafts and/or caveolin-1. Upon internalization, soluble glucans are trafficked via endosomes to the Golgi apparatus, not lysosomes.
Department of Surgery, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614-0575, USA. ozmentsk@etsu.edu
Tammy R
TR
Ozment
Matthew P
MP
Goldman
John H
JH
Kalbfleisch
David L
DL
Williams
D000818:Animals; D002966:Clathrin / Q000235:genetics / Q000378:metabolism*; D011992:Endosomes / Q000235:genetics / Q000378:metabolism; D005936:Glucans / Q000235:genetics / Q000378:metabolism* / Q000493:pharmacokinetics; D006056:Golgi Apparatus / Q000235:genetics / Q000378:metabolism*; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism; D008055:Lipids / Q000235:genetics; D008247:Lysosomes / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D021381:Protein Transport; D000099181:Dectin-1
D002966:Clathrin; D005936:Glucans; D037181:Lectins, C-Type; D008055:Lipids; D000099181:Dectin-1