Proteomic Profiling of LPS‐Induced Macrophage‐Derived Exosomes Indicates Their Involvement in Acute Liver Injury

Abstract Exosomes are typically involved in cellular communication and signaling. Macrophages play a key role in lipopolysaccharide (LPS)‐induced sepsis. However, the molecular comparison of exosomes derived from LPS‐induced macrophage has not been well analyzed. The macrophage‐exosomes are validated and the protein composition of those exosomes are investigated by isobaric tags for relative and absolute quantification (iTRAQ) mass spectrometry. A total of 5056 proteins are identified in macrophage‐exosomes. We discovered 341 increased proteins and 363 reduced proteins in LPS‐treated macrophage‐exosomes compared with control exosomes. In addition, gene ontology analysis demonstrates that macrophage‐exosomes proteins are mostly linked to cell, organelle, extracellular region, and membrane. The bioinformatics analysis also indicates that these proteins are mainly involved in cellular process, single‐organism process, metabolic process, and biological regulation. Among these 341 upregulated proteins, Kyoto Encyclopedia of Genes and Genomes analysis reveals that 22 proteins are involved in the NOD‐like receptor signaling pathway. Finally, hepatocytes can uptake macrophage‐exosomes and subsequently NLRP3 inflammasome is activated in vitro and in vivo. These data emphasize the fundamental importance of macrophage‐exosomes in sepsis‐induced liver injury. Therefore, the iTRAQ proteomic strategy brings new insights into macrophage‐derived exosomes. It may improve our understanding of macrophage‐exosomes’ functions and their possible use as therapeutic targets for sepsis.