期刊
EUROPEAN JOURNAL OF CELL BIOLOGY
卷 89, 期 9, 页码 693-704出版社
ELSEVIER GMBH, URBAN & FISCHER VERLAG
DOI: 10.1016/j.ejcb.2010.04.006
关键词
Phagocytosis; Receptor-ligand interaction; Macrophage; Phagosome maturation; Phagocytic receptor; Phagosomal proteome; Gene expression; Signaling pathways; Immune response
类别
资金
- Deutsche Forschungsgemeinschaft (DFG) [KU1528/2]
- EU commission Marie Curie Research Training Network [MRTN-CT-2006-035946]
- AXA Research Fund
- Pratt Committee of the University of Virginia, USA
The receptors engaged during recognition and phagocytic uptake of microorganisms and particles influence signaling events and diverse subcellular responses that occur during phagosome formation and maturation. However, pathogens generally have multiple ligands on their surface, making it difficult to dissect the roles of individual receptors during phagocytosis. Moreover, it remains elusive to which extent receptor-ligand interactions and early binding events define the subsequent intracellular fate of phagosomes. Here, we used latex beads coupled to single ligands, focusing on immunoglobulin G, mannan, bacterial lipopolysaccharides and avidin, and monitored: (1) phagocytic uptake rates, (2) fusion of phagosomes with lysosomal compartments, (3) the gene expression profile during phagocytosis, (4) the protein composition of mature phagosomes and (5) time-dependent dynamics of protein association with phagosomes in J774.A1 mouse macrophages. The differently coated latex beads were internalized at different rates and exhibited different kinetics of phagolysosomal fusion events dependent on their specific ligand. Furthermore, less than 60% of identified phagosomal proteins and only 10-15% of changes in gene expression were common to all investigated ligands. These findings demonstrate that each single ligand induced a distinct pattern of genes and a different protein composition of phagosomes. Taken together, our data argue that phagocytic receptor-specific programs of signaling events direct phagosomes to different physiological states and support the existence of a specific receptor-ligand 'signature' during the whole process of phagocytosis. (C) 2010 Elsevier GmbH. All rights reserved.
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