Abstract
Macrophages, as professional phagocytes of the immune system, possess the ability to detect and clear invading pathogens and apoptotic cells through phagocytosis. Phagocytosis involves membrane reorganization and remodeling events on the cell surface, which play an essential role in innate immunity and tissue homeostasis and the control of inflammation. In this work, we report that cells deficient in membrane ethanolamine plasmalogen demonstrate a reduced capacity to phagocytize opsonized zymosan particles. Amelioration of plasmalogen deficiency in these cells by incubation with lysoplasmalogen results in a significant augmentation of the phagocytic capacity of the cells. In parallel with these increases, restoration of plasmalogen levels in the cells also increases the number and size of lipid rafts in the membrane, reduces membrane fluidity down to levels found in cells containing normal plasmalogen levels, and improves receptor-mediated signaling. Collectively, these results suggest that membrane plasmalogen level determines characteristics of the plasma membrane such as fluidity and the formation of microdomains that are necessary for efficient signal transduction leading to optimal phagocytosis by macrophages.
Highlights
Macrophages play key functions in innate and inflammation by clearing pathogens, damaged cells, and debris via highly regulated phagocytosis processes, which aim at efficiently restoring tissue homeostasis [1, 2]
Taking advantage as well of the use of plasmalogen-deficient cells [42, 43], we show that reduction in plasmalogen levels leads to altered phagocytosis of opsonized zymosan (OpZ) particles by macrophages which can be attributed to changes in the plasma membrane fluidity and the formation and functioning of the lipid rafts
In previous work from our laboratory, we demonstrated that phospholipase A2-mediated hydrolysis of ethanolamine-containing phospholipids at the membrane is a key event to support phagocytosis of yeast-derived zymosan and live bacteria by human macrophages [40]
Summary
Macrophages play key functions in innate and inflammation by clearing pathogens, damaged cells, and debris via highly regulated phagocytosis processes, which aim at efficiently restoring tissue homeostasis [1, 2]. To carry out this function, macrophages are endowed with a variety of cell surface receptors, collectively called opsonin-independent receptors, which include the C-type lectins such as dectin-1 and the mannose receptor; scavenger receptors such as SR-A-I, SR-A-II, MARCO, and CD36; and toll-like receptors such as TLR-2 and TLR-6 [3,4,5,6]. Engagement of phagocytic receptors, both non-opsonic and opsonic, triggers the synthesis and release of an ample variety of mediators such as cytokines, chemokines, and arachidonic acid-derived eicosanoids that regulate the inflammatory response [3,4,5,6,7,8].
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