Exosomes derived from human macrophages suppress endothelial cell migration by controlling integrin trafficking
| Autor: | Hee Doo, Lee, Yeon Hyang, Kim, Doo-Sik, Kim |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
MAP Kinase Signaling System
Integrin beta1 Macrophages Immunoblotting Down-Regulation Exosomes Endocytosis Protein Transport HEK293 Cells Cell Movement Cell Line Tumor Human Umbilical Vein Endothelial Cells Microscopy Electron Scanning Humans RNA Interference Mitogen-Activated Protein Kinases Phosphorylation Lysosomes Cells Cultured |
| Zdroj: | European journal of immunology. 44(4) |
| ISSN: | 1521-4141 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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