Endogenous galectin-3 is localized in membrane lipid rafts and regulates migration of dendritic cells.
This study reveals a function of endogenous galectin-3, an animal lectin recognizing beta-galactosides, in regulating dendritic cell motility both in vitro and in vivo, which to our knowledge is unreported. First, galectin-3-deficient (gal3(-/-)) bone marrow-derived dendritic cells exhibited defective chemotaxis compared to gal3(+/+) cells. Second, cutaneous dendritic cells in gal3(-/-) mice displayed reduced migration to draining lymph nodes upon hapten stimulation compared to gal3(+/+) mice. Moreover, gal3(-/-) mice were impaired in the development of contact hypersensitivity relative to gal3(+/+) mice in response to a hapten, a process in which dendritic cell trafficking to lymph nodes is critical. In addition, defective signaling was detected in gal3(-/-) cells upon chemokine receptor activation. By immunofluorescence microscopy, we observed that galectin-3 is localized in membrane ruffles and lamellipodia in stimulated dendritic cells and macrophages. Furthermore, galectin-3 was enriched in lipid raft domains under these conditions. Finally, we determined that ruffles on gal3(-/-) cells contained structures with lower complexity compared to gal3(+/+) cells. In view of the participation of membrane ruffles in signal transduction and cell motility, we conclude that galectin-3 regulates cell migration by functioning at these structures.
Hsu
Daniel K
DK
Department of Dermatology, University of California Davis School of Medicine, Sacramento, California 95817, USA. dkhsu@ucdavis.edu
Chernyavsky
Alexander I
AI
Chen
Huan-Yuan
HY
Yu
Lan
L
Grando
Sergei A
SA
Liu
Fu-Tong
FT
D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism; D002633:Chemotaxis; D003713:Dendritic Cells / Q000378:metabolism*; D037502:Galectin 3 / Q000096:biosynthesis* / Q000737:chemistry; D008198:Lymph Nodes / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D021962:Membrane Microdomains / Q000737:chemistry*; D051379:Mice; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D015398:Signal Transduction
D018925:Chemokines; D037502:Galectin 3