{"doi":"10.64898/2025.12.09.693266","title":"LPC 18:2-Driven Apoptosis In Neutrophils Is Non-Inflammatory and Lipid Raft Dependent","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.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":556937,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9586,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1099618,"name":"Alicia Gibbons","orcid":"0000-0003-0567-375X","position":1,"is_corresponding":false},{"id":239474,"name":"Ian T. Mathews","orcid":"0000-0003-4773-7985","position":2,"is_corresponding":false},{"id":1456629,"name":"Maija Corey","orcid":"0000-0002-3470-9806","position":3,"is_corresponding":false},{"id":501588,"name":"Ashmitaa Logandha Ramamoorthy Premlal","orcid":"0000-0001-7110-4235","position":4,"is_corresponding":false},{"id":1456630,"name":"Mahati Rayadurgam","orcid":"0009-0009-5206-6312","position":5,"is_corresponding":false},{"id":1331224,"name":"Namratha Nadig","orcid":"0009-0001-1150-9449","position":6,"is_corresponding":false},{"id":1456631,"name":"Camille Fang","orcid":"0009-0004-8814-7732","position":7,"is_corresponding":false},{"id":1456632,"name":"Neha Reddy","orcid":"0000-0002-6599-0098","position":8,"is_corresponding":false},{"id":1456633,"name":"Mousa Vatanmakanian","orcid":"0009-0009-2630-7119","position":9,"is_corresponding":false},{"id":246517,"name":"Sonia Sharma","orcid":"0000-0002-6556-1963","position":10,"is_corresponding":false},{"id":272238,"name":"Priyanka Saminathan","orcid":"0000-0001-8367-2811","position":0,"is_corresponding":true}],"reference_count":52,"raw_metadata":null,"created_at":"2026-07-19T02:55:13.130091Z","pmid":"41427411","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}