Citation

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 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. Renitence vacuoles formed coincident with silica bead uptake in a process associated with membrane ruffling and macropinocytosis. However, unlike normal macropinosomes, which shrink within 20 minutes of formation, renitence vacuoles persisted around bead-containing phagosomes. Renitence vacuoles fused with lysosomes, whereas associated phagosomes typically did not. These findings are consistent with a model in which renitence vacuoles, as persistent macropinosomes, prevent fusion between damaged phagosomes and intact lysosomes and thereby preserve endolysosomal integrity.