Plasmalogens in Innate Immune Cells: From Arachidonate Signaling to Ferroptosis

Area of Science:

• Biochemistry
• Cell Biology
• Immunology

Background:

• Polyunsaturated fatty acids (PUFAs), including arachidonic acid, are vital for innate immune signaling.
• Plasmalogens are unique phospholipids characterized by a vinyl ether bond at the sn-1 position, distinguishing them from classical glycerophospholipids.
• These phospholipids are abundant in PUFAs, particularly arachidonic acid.

Purpose of the Study:

• To review recent data on the multifaceted roles of plasmalogens beyond their contribution to arachidonic acid metabolism.
• To highlight the importance of plasmalogens in cellular functions such as membrane dynamics and cell death pathways.

Main Methods:

• Review of existing scientific literature and data.
• Analysis of the structural and functional properties of plasmalogens.
• Discussion of plasmalogen involvement in immune signaling, membrane biophysics, and ferroptosis.

Main Results:

• Plasmalogens serve as a significant source of free arachidonic acid for eicosanoid synthesis.
• Membrane plasmalogen levels influence plasma membrane fluidity and microdomain formation, critical for macrophage phagocytosis.
• Plasmalogens are implicated in the execution of ferroptosis, a form of oxidative stress-induced cell death.

Conclusions:

• Cells maintain stable pools of PUFA-rich plasmalogens for specific cellular responses.
• Plasmalogens have diverse functions in innate immunity, cell signaling, membrane integrity, and programmed cell death.
• Further research into plasmalogen functions is warranted to fully understand their biological significance.