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2017 ; 8
(5
): 7420-7440
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Comprehensive proteome analysis of lysosomes reveals the diverse function of
macrophages in immune responses
#MMPMID28088779
Gao Y
; Chen Y
; Zhan S
; Zhang W
; Xiong F
; Ge W
Oncotarget
2017[Jan]; 8
(5
): 7420-7440
PMID28088779
show ga
Phagocytosis and autophagy in macrophages have been shown to be essential to both
innate and adaptive immunity. Lysosomes are the main catabolic subcellular
organelles responsible for degradation and recycling of both extracellular and
intracellular material, which are the final steps in phagocytosis and autophagy.
However, the molecular mechanisms underlying lysosomal functions after infection
remain obscure. In this study, we conducted a quantitative proteomics analysis of
the changes in constitution and glycosylation of proteins in lysosomes derived
from murine RAW 264.7 macrophage cells treated with different types of pathogens
comprising examples of bacteria (Listeria monocytogenes, L. m), DNA viruses
(herpes simplex virus type-1, HSV-1) and RNA viruses (vesicular stomatitis virus,
VSV). In total, 3,704 lysosome-related proteins and 300 potential glycosylation
sites on 193 proteins were identified. Comparative analysis showed that the
aforementioned pathogens induced distinct alterations in the proteome of the
lysosome, which is closely associated with the immune functions of macrophages,
such as toll-like receptor activation, inflammation and antigen-presentation. The
most significant changes in proteins and fluctuations in glycosylation were also
determined. Furthermore, Western blot analysis showed that the changes in
expression of these proteins were undetectable at the whole cell level. Thus, our
study provides unique insights into the function of lysosomes in macrophage
activation and immune responses.