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Phospholipid signaling in innate immune cells
Valerie B. O’Donnell, … , Jamie Rossjohn, Michael J.O. Wakelam
Valerie B. O’Donnell, … , Jamie Rossjohn, Michael J.O. Wakelam
Published April 23, 2018
Citation Information: J Clin Invest. 2018;128(7):2670-2679. https://doi.org/10.1172/JCI97944.
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Review Series

Phospholipid signaling in innate immune cells

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Abstract

Phospholipids comprise a large body of lipids that define cells and organelles by forming membrane structures. Importantly, their complex metabolism represents a highly controlled cellular signaling network that is essential for mounting an effective innate immune response. Phospholipids in innate cells are subject to dynamic regulation by enzymes, whose activities are highly responsive to activation status. Along with their metabolic products, they regulate multiple aspects of innate immune cell biology, including shape change, aggregation, blood clotting, and degranulation. Phospholipid hydrolysis provides substrates for cell-cell communication, enables regulation of hemostasis, immunity, thrombosis, and vascular inflammation, and is centrally important in cardiovascular disease and associated comorbidities. Phospholipids themselves are also recognized by innate-like T cells, which are considered essential for recognition of infection or cancer, as well as self-antigens. This Review describes the major phospholipid metabolic pathways present in innate immune cells and summarizes the formation and metabolism of phospholipids as well as their emerging roles in cell biology and disease.

Authors

Valerie B. O’Donnell, Jamie Rossjohn, Michael J.O. Wakelam

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Figure 2

PL cleavage and PL asymmetry in innate immune cells.

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PL cleavage and PL asymmetry in innate immune cells.
(A) Phospholipases ...
(A) Phospholipases PLA1, PLA2, PLC, and PLD hydrolyze PLs and are named by the site of hydrolysis, as shown. (B) Flippase and floppase enzymes maintain membrane symmetry on resting platelet membranes. Upon activation, calcium-dependent externalization of PE and PS provides a negatively charged surface that supports coagulation factor binding and facilitates prothrombin’s conversion to active thrombin. X and V, zymogen coagulation factors X and V; Xa/Va, a complex of activated factor X and factor V (prothrombinase complex).

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