Integrin trafficking, including internalization, recycling, and lysosomal 
degradation, is crucial for the regulation of cellular functions. Exosomes, 
nano-sized extracellular vesicles, are believed to play important roles in 
intercellular communications. This study demonstrates that exosomes released 
from human macrophages negatively regulate endothelial cell migration through 
control of integrin trafficking. Macrophage-derived exosomes promote 
internalization of integrin β1 in primary HUVECs. The internalized integrin β1 
persistently accumulates in the perinuclear region and is not recycled back to 
the plasma membrane. Experimental results indicate that macrophage-derived 
exosomes stimulate trafficking of internalized integrin β1 to lysosomal 
compartments with a corresponding decrease in the integrin destined for 
recycling endosomes, resulting in proteolytic degradation of the integrin. 
Moreover, ubiquitination of HUVEC integrin β1 is enhanced by the exosomes, and 
exosome-mediated integrin degradation is blocked by bafilomycin A, a lysosomal 
degradation inhibitor. Macrophage-derived exosomes were also shown to 
effectively suppress collagen-induced activation of the mitogen-activated 
protein kinase/extracellular signal-regulated kinase signaling pathway and HUVEC 
migration, which are both dependent on integrin β1. These observations provide 
new insight into the functional significance of exosomes in the regulation of 
integrin trafficking.