Renitence vacuoles facilitate protection against phagolysosomal damage in activated macrophages
| Autor: | Brian Gregorka, Amanda O. Wong, Michele S. Swanson, Joel A. Swanson, Matangi Marthi, Zachary I. Mendel |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Lipopolysaccharides Membrane ruffling Lipopolysaccharide Phagocytosis Kinetics Endolysosomal membrane Vacuole Endosomes Biology 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Phagosomes Animals Molecular Biology Phagosome Pinocytosis Macrophages Cell Biology Intracellular Membranes Cell biology Mice Inbred C57BL 030104 developmental biology chemistry Vacuoles Lysosomes 030215 immunology |
| Zdroj: | Molecular biology of the cell. 29(5) |
| ISSN: | 1939-4586 |
| Popis: | As professional phagocytes, macrophages are susceptible to endolysosomal membrane damage inflicted by the pathogens and noxious particles they ingest. Whether macrophages have mechanisms for limiting such damage is not well understood. Previously, we reported a phenomenon, termed “inducible renitence,” in which lipopolysaccharide (LPS) activation of macrophages protected their endolysosomes against damage initiated by the phagocytosis of silica beads. To gain mechanistic insight into the process, we analyzed the kinetics of renitence and morphological features of LPS-activated versus resting macrophages following silica bead–mediated injury. We discovered novel vacuolar structures that form in LPS-activated but not resting macrophages following silica bead phagocytosis. Because of their correlation with renitence and damage-resistant nature, we termed these structures “renitence vacuoles” (RVs). RVs formed coincident with silica bead uptake in a process associated with membrane ruffling and macropinocytosis. However, unlike normal macropinosomes (MPs), which shrink within 20 min of formation, RVs persisted around bead-containing phagosomes. RVs fused with lysosomes, whereas associated phagosomes typically did not. These findings are consistent with a model in which RVs, as persistent MPs, prevent fusion between damaged phagosomes and intact lysosomes and thereby preserve endolysosomal integrity. |
| Databáze: | OpenAIRE |
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