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bioRxiv · 10.64898/2025.12.09.693266

LPC 18:2-Driven Apoptosis In Neutrophils Is Non-Inflammatory and Lipid Raft Dependent

Saminathan, P.·Gibbons, A.·Mathews, I.·Corey, M. Y.·Logandha, A.·Rayadurgam, M.·Nadig, N.·Fang, C.·Reddy, N.·Vatanmakanian, M.·Sharma, S.
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Abstract

Lysophosphatidylcholines (LPCs) are potent bioactive lipids whose fatty acid compositions dictate their immunomodulatory effects. Here, we delineate how unsaturated LPC 18:2 and saturated LPC 16:0 differentially regulate neutrophil survival and inflammatory programs. LPC 18:2 markedly increased reactive oxygen species (ROS) generation and caspase-3/7 activation, mitochondrial membrane depolarization, and cytochrome c release, features consistent with intrinsic apoptosis. In contrast, LPC 16:0 induced robust LDH and HMGB-1 release, indicating membrane rupture and pyroptosis-like death. Bulk RNA sequencing revealed that LPC 16:0 strongly upregulated inflammatory and cytokine gene expression. Disruption of lipid-raft integrity abolished LPC 18:2-induced ROS and apoptosis, underscoring the dependence of these effects on membrane organization. Collectively, these results identify LPC 18:2 as a non-inflammatory, mitochondria-dependent inducer of neutrophil apoptosis, whereas LPC 16:0 promotes inflammatory, lytic death programs. These findings highlight how lipid saturation determines neutrophil fate and immune tone, providing mechanistic insight into how distinct LPC species shape inflammation and tissue injury.

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Saminathan, P., Gibbons, A., Mathews, I., Corey, M. Y., Logandha, A., Rayadurgam, M., Nadig, N., Fang, C., Reddy, N., Vatanmakanian, M., Sharma, S.. 2025-12-12. LPC 18:2-Driven Apoptosis In Neutrophils Is Non-Inflammatory and Lipid Raft Dependent. https://doi.org/10.64898/2025.12.09.693266

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