TY - JOUR
T1 - The Roles of Phospholipase A2 in Phagocytes
AU - Dabral, Deepti
AU - van den Bogaart, Geert
N1 - Funding Information:
Funding. GB is funded by a Young Investigator Grant from the Human Frontier Science Program (HFSP; RGY0080/2018). GB has received funding from the European Research Council (ERC) under the European Union?s Horizon 2020 Research and Innovation Program (Grant Agreement No. 862137).
Publisher Copyright:
© Copyright © 2021 Dabral and van den Bogaart.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/6/10
Y1 - 2021/6/10
N2 - Phagocytic cells, such as macrophages, neutrophils, and dendritic cells, ingest particles larger than about 0.5 μM and thereby clear microbial pathogens and malignant cells from the body. These phagocytic cargoes are proteolytically degraded within the lumen of phagosomes, and peptides derived from them are presented on Major Histocompatibility Complexes (MHC) for the activation of T cells. Mammalian PLA2 isozymes belong to a large family of enzymes that cleave phospholipids at the second position of the glycerol backbone, releasing a free fatty acid and a lysolipid moiety. In human macrophages, at least 15 different PLA2 forms are expressed, and expression of many of these is dependent on pathogenic stimulation. Intriguing questions are why so many PLA2 forms are expressed in macrophages, and what are the functional consequences of their altered gene expression after encountering pathogenic stimuli. In this review, we discuss the evidence of the differential roles of different forms of PLA2 in phagocytic immune cells. These roles include: lipid signaling for immune cell activation, initial phagocytic particle uptake, microbial action for the killing and degradation of ingested microbes, and the repair of membranes induced by oxygen radicals. We also discuss the roles of PLA2 in the subsequent digestion of ingested phagocytic cargoes for antigen presentation to T cells.
AB - Phagocytic cells, such as macrophages, neutrophils, and dendritic cells, ingest particles larger than about 0.5 μM and thereby clear microbial pathogens and malignant cells from the body. These phagocytic cargoes are proteolytically degraded within the lumen of phagosomes, and peptides derived from them are presented on Major Histocompatibility Complexes (MHC) for the activation of T cells. Mammalian PLA2 isozymes belong to a large family of enzymes that cleave phospholipids at the second position of the glycerol backbone, releasing a free fatty acid and a lysolipid moiety. In human macrophages, at least 15 different PLA2 forms are expressed, and expression of many of these is dependent on pathogenic stimulation. Intriguing questions are why so many PLA2 forms are expressed in macrophages, and what are the functional consequences of their altered gene expression after encountering pathogenic stimuli. In this review, we discuss the evidence of the differential roles of different forms of PLA2 in phagocytic immune cells. These roles include: lipid signaling for immune cell activation, initial phagocytic particle uptake, microbial action for the killing and degradation of ingested microbes, and the repair of membranes induced by oxygen radicals. We also discuss the roles of PLA2 in the subsequent digestion of ingested phagocytic cargoes for antigen presentation to T cells.
KW - macrophages
KW - pathogens
KW - phagocytosis
KW - PLA
KW - trafficking
UR - http://www.scopus.com/inward/record.url?scp=85108893193&partnerID=8YFLogxK
U2 - 10.3389/fcell.2021.673502
DO - 10.3389/fcell.2021.673502
M3 - Review article
AN - SCOPUS:85108893193
SN - 2296-634X
VL - 9
JO - Frontiers in Cell and Developmental Biology
JF - Frontiers in Cell and Developmental Biology
M1 - 673502
ER -