Galectin-3 functions as an opsonin and enhances the macrophage clearance of apoptotic neutrophils.
Galectin-3, a beta-galactoside binding, endogenous lectin, takes part in various inflammatory events and is produced in substantial amounts at inflammatory foci. We investigated whether extracellular galectin-3 could participate in the phagocytic clearance of apoptotic neutrophils by macrophages, a process of crucial importance for termination of acute inflammation. Using human leukocytes, we show that exogenously added galectin-3 increased the uptake of apoptotic neutrophils by monocyte-derived macrophages (MDM). Both the proportion of MDM that engulfed apoptotic prey and the number of apoptotic neutrophils that each MDM engulfed were enhanced in the presence of galectin-3. The effect was lactose-inhibitable and required galectin-3 affinity for N-acetyllactosamine, a saccharide typically found on cell surface glycoproteins, since a mutant lacking this activity was without effect. The enhanced uptake relied on the presence of galectin-3 during the cellular interaction and was paralleled by lectin binding to apoptotic cells as well as MDM in a lactose-dependent manner. These findings suggest that galectin-3 functions as a bridging molecule between phagocyte and apoptotic prey, acting as an opsonin. The process of clearance, whereby apoptotic neutrophils are removed by macrophages, is crucial for the resolution of acute inflammation and our data imply that the increased levels of galectin-3 often found at inflammatory sites could potently affect this process.
Karlsson
Anna
A
Department of Rheumatology and Inflammation Research, University of Gothenburg, Sweden.
Christenson
Karin
K
Matlak
Mustafa
M
Björstad
Ase
A
Brown
Kelly L
KL
Telemo
Esbjörn
E
Salomonsson
Emma
E
Leffler
Hakon
H
Bylund
Johan
J
D017209:Apoptosis / Q000276:immunology*; D001665:Binding Sites; D002478:Cells, Cultured; D037502:Galectin 3 / Q000378:metabolism*; D006801:Humans; D008262:Macrophage Activation; D008264:Macrophages / Q000378:metabolism*; D009504:Neutrophils / Q000378:metabolism*; D009895:Opsonin Proteins / Q000378:metabolism*
D037502:Galectin 3; D009895:Opsonin Proteins