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Record W4404501647 · doi:10.1101/2024.11.18.624161

Phosphatidylethanolamine is a phagocytic ligand implicated in the binding and removal of apoptotic and microbial extracellular vesicles

2024· preprint· en· W4404501647 on OpenAlexaff
Ava A Kavianpour, Sina Ghasempour, Kirsten J. Meyer, Trieu Le, Ruiqi Cai, Pedro Elias Marques, Justin R. Nodwell, Spencer A. Freeman

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2024
Typepreprint
Languageen
FieldImmunology and Microbiology
TopicPhagocytosis and Immune Regulation
Canadian institutionsUniversity of TorontoHospital for Sick Children
Fundersnot available
KeywordsPhosphatidylethanolamineExtracellular vesiclesExtracellularCell biologyChemistryLigand (biochemistry)VesicleMicrobiologyBiochemistryBiophysicsReceptorBiologyMembranePhosphatidylcholinePhospholipid

Abstract

fetched live from OpenAlex

Abstract The efficient recognition and removal of apoptotic cells by phagocytes is critical to prevent secondary necrosis and maintain tissue homeostasis. Such detection involves receptors and bridging molecules that recognize lipids −normally restricted to the inner leaflet of healthy cells− which become exposed on the surface of dead cells and the vesicles they produce. A majority of studies focus on phosphatidylserine (PS) for which there are well-established receptors that either bind to the lipid directly or indirectly via intermediary proteins. Phosphatidylethanolamine (PE) is even more prevalent than PS in the inner leaflet of mammalian cells and also becomes exposed by the action of scramblases during cell death, though little is known about the effects of PE once scrambled. Here, we report that PE can itself serve as a phagocytic ligand for macrophages by engaging CD300 family receptors. CD300a and CD300b specifically modulated PE-mediated uptake, and this process involved ITAM-containing adaptors and the spleen tyrosine kinase (Syk). For bacteria, which contain PE but largely lack PS in their membranes, we report that PE engagement enabled the binding and uptake of spheroplasts and extracellular vesicles (EVs) that were unsheathed by the cell wall. The inflammatory responses of macrophages to PE particles containing LPS was also curtailed by CD300a expression. Based on these observations, we posit that the direct recognition of PE facilitates mechanisms of clearance that stand to have a broad impact on the immune response.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.000

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.001

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.013
GPT teacher head0.219
Teacher spread0.206 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations0
Published2024
Admission routes1
Has abstractyes

Explore more

Same venuebioRxiv (Cold Spring Harbor Laboratory)Same topicPhagocytosis and Immune RegulationFrench-language works237,207