ArticleThe Journal of biological chemistry2014
A cleavage-potentiated fragment of tear lacritin is bactericidal.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06854393 (Lacripep, a Novel Investigational Agent, for Corneal Wound Healing and Ocular Surface Homeostasis), which is not on this map. Cited by 26 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Lacripep, a Novel Investigational Agent, for Corneal Wound Healing and Ocular Surface Homeostasis
Who cites it
26 citing papers in PubMed, 32 citations in OpenAlex.
- Site-specific O-glycans influence lacritin structure and multimerization in tears.Protein science : a publication of the Protein Society · 2026Article
- Distinctive Lacritin Cleavage-Potentiated Bactericidal Alteration of thebioRxiv : the preprint server for biology · 2026Article
- Article
- Mapping galectin-3 ligands in human tear fluid establishes spliceoform-dependent lacritin binding.Communications biology · 2026Article
- Lacritin cleavage-potentiated targeting of iron - respiratory reciprocity promotes bacterial death.The Journal of biological chemistry · 2025Article
- Targeting Iron - Respiratory Reciprocity Promotes Bacterial Death.bioRxiv : the preprint server for biology · 2024Article
- Salivary Chemical Barrier Proteins in Oral Squamous Cell Carcinoma-Alterations in the Defense Mechanism of the Oral Cavity.International journal of molecular sciences · 2023Article
- Lectin-Based Affinity Enrichment and Characterization of N-Glycoproteins from Human Tear Film by Mass Spectrometry.Molecules (Basel, Switzerland) · 2023Article
- Chemical Barrier Proteins in Human Body Fluids.Biomedicines · 2022Review
- Foundational concepts in the biology of bacterial keratitis.Experimental eye research · 2021Review
- Reduced Level of Tear Antimicrobial and Immunomodulatory Proteins as a Possible Reason for Higher Ocular Infections in Diabetic Patients.Pathogens (Basel, Switzerland) · 2021Article
- The Role of Endogenous Antimicrobial Peptides in Modulating Innate Immunity of the Ocular Surface in Dry Eye Diseases.International journal of molecular sciences · 2021Review
- Development of a Quantitative Immunoassay for Tear Lacritin Proteoforms.Translational vision science & technology · 2020Article
- The Lacritin-Syndecan-1-Heparanase Axis in Dry Eye Disease.Advances in experimental medicine and biology · 2020Review
- Tasked with a Challenging Objective: Why Do Neutrophils Fail to BattlePathogens (Basel, Switzerland) · 2019Review
- Autophagy and Age-Related Eye Diseases.BioMed research international · 2019Review
- Human Antimicrobial Peptides in Bodily Fluids: Current Knowledge and Therapeutic Perspectives in the Postantibiotic Era.Medicinal research reviews · 2018Review
- Article
- Characterisation of the immune compounds in koala milk using a combined transcriptomic and proteomic approach.Scientific reports · 2016Article
- Reduced Levels of Tear Lacritin Are Associated With Corneal Neuropathy in Patients With the Ocular Component of Sjögren's Syndrome.Investigative ophthalmology & visual science · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Antimicrobial peptides are important as the first line of innate defense, through their tendency to disrupt bacterial membranes or intracellular pathways and potentially as the next generation of antibiotics. How they protect wet epithelia is not entirely clear, with most individually inactive under physiological conditions and many preferentially targeting Gram-positive bacteria. Tears covering the surface of the eye are bactericidal for Gram-positive and -negative bacteria. Here we narrow much of the bactericidal activity to a latent C-terminal fragment in the prosecretory mitogen lacritin and report that the mechanism combines membrane permeabilization with rapid metabolic changes, including reduced levels of dephosphocoenzyme A, spermidine, putrescine, and phosphatidylethanolamines and elevated alanine, leucine, phenylalanine, tryptophan, proline, glycine, lysine, serine, glutamate, cadaverine, and pyrophosphate. Thus, death by metabolic stress parallels cellular attempts to survive. Cleavage-dependent appearance of the C-terminal cationic amphipathic α-helix is inducible within hours by Staphylococcus epidermidis and slowly by another mechanism, in a chymotrypsin- or leupeptin protease-inhibitable manner. Although bactericidal at low micromolar levels, within a biphasic 1-10 nM dose optimum, the same domain is mitogenic and cytoprotective for epithelia via a syndecan-1 targeting mechanism dependent on heparanase. Thus, the C terminus of lacritin is multifunctional by dose and proteolytic processing and appears to play a key role in the innate protection of the eye, with wider potential benefit elsewhere as lacritin flows from exocrine secretory cells.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.