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Published on: February 22, 2019
[Profiles of intracellular expression, distribution, and activation of phospholipase A2 in host macrophages infected
Chiaki Sano1, Toshiaki Shimizu, Yutaka Tatano
1Department of Microbiology and Immunology, Shimane University School of Medicine.
Abstract:
Our recent studies have shown that type IV cytosolic phospholipase A2 (cPLA2) plays an important role in the expression of macrophage (MPh) antimicrobial activity against the Mycobacterium avium complex (MAC). To clarify the modes of cPLA2 participation in MPh anti-MAC antimicrobial function in detail, we studied intracellular profiles of phospholilase A2, focusing on cPLA2, in MAC-infected MPhs, with the following findings: In murine peritoneal MPhs, cPLA2 was constitutively expressed even in uninfected MPhs, and MAC infection did not increase intramacrophage cPLA2 expression. In an RAW264.7 mouse MPh cell line (RAW264.7 MPhs) infected with MAC, a portion of intracellular cPLA2 was concentrated in MAC organisms residing within MPh phagosomes. MAC infection upregulated intramacrophage cPLA2 expression and induced its phosphorylation. These findings suggest that MAC infection of RAW264.7 MPhs may induce the activation of intracellular cPLA2, translocating it to phagosomes engulfing infected MAC organisms.
Insights
Type IV cytosolic phospholipase A2 (cPLA2) is crucial for macrophage antimicrobial activity against Mycobacterium avium complex (MAC). In RAW264.7 cells, MAC infection activates and concentrates cPLA2 within phagosomes containing the bacteria.
Area of Science:
- Immunology
- Cell Biology
- Microbiology
Context:
- Macrophages (MPh) are key immune cells involved in combating intracellular pathogens.
- Mycobacterium avium complex (MAC) is an opportunistic pathogen that infects macrophages.
- Type IV cytosolic phospholipase A2 (cPLA2) has been implicated in macrophage antimicrobial functions.
Purpose:
- To elucidate the detailed mechanisms of cPLA2 involvement in macrophage anti-MAC activity.
- To investigate the intracellular localization and expression patterns of cPLA2 during MAC infection in macrophages.
Summary:
- In murine peritoneal macrophages, cPLA2 is constitutively expressed and not upregulated by MAC infection.
- In RAW264.7 macrophages, MAC infection leads to increased intracellular cPLA2 expression and phosphorylation.
- A portion of activated cPLA2 translocates to phagosomes containing MAC organisms within RAW264.7 macrophages.
Impact:
- These findings suggest a novel activation and recruitment mechanism for cPLA2 in macrophage phagosomes during MAC infection.
- Understanding cPLA2 dynamics provides insights into host-pathogen interactions and potential therapeutic targets for MAC infections.
