L‐Citrulline Modulates Macrophage Polarization to an M2 Phenotype in a Model of Lipopolysaccharide‐Induced Lung Injury in Neonatal Rats
Notice bibliographique
Résumé
Introduction Bronchopulmonary dysplasia (BPD), a chronic lung disease in premature infants resulting from inflammation and oxidative stress, leads to arrested pulmonary development and lifelong respiratory morbidities. Macrophages are the most abundant immune cells in the neonatal lung, orchestrating inflammation, maintaining homeostasis, and supporting tissue remodeling and repair. Macrophages can polarize into specific phenotypes in response to the micro‐environment. M1 macrophages are pro‐inflammatory and pathogen killing whereas, M2 macrophages are anti‐inflammatory and support normal lung development. Existing therapies for BPD have inherent side effects. L‐Citrulline (L‐CIT), a non‐essential amino acid, that is safe and well‐tolerated by infants, reduces oxidative stress and lung inflammation. Thus, we hypothesize that L‐CIT modulates macrophage polarization to an M2 phenotype in the presence of lipopolysaccharide (LPS) induced lung injury during early development. Methods Sprague Dawley rat pups received saline (SAL) or L‐CIT (2.5 g/kg) intraperitoneally during postnatal day (PND) 4‐9. In addition, pups were treated with LPS (5mg/kg) or SAL intrapharyngeally during PND 5‐8. Thus, we had 4 treatment groups, ie., SAL+SAL (controls), LPS+SAL, LPS+L‐CIT and L‐CIT+SAL. Pups were euthanized on PND 9. Bronchoalveolar Lavage Fluid (BALF) : BALF was cytospinned, and cells were counted following hematoxylin and eosin staining. BALF supernatant was collected, and an arginase activity assay was performed for M2 marker expression. Lung homogenate : Lungs were dissected, homogenized and processed for western blotting of M2 (CD206) and M1 (Arg2) markers normalized to rat macrophage marker (F4/80). Results BALF analysis: The number of alveolar macrophages infiltrated in the BALF of animals treated with L‐CIT+LPS (n=4) and those treated with SAL+LPS (n=4) were similar; both were significantly higher than control (p<.001; p<.0001, respectively). Arginase activity in the BALF was significantly higher in animals treated with L‐CIT+LPS (p<.05; n= 4) compared to LPS alone (p<.05; n=4). Lung homogenate analysis : LPS+SAL treated animals had lower levels of protein expression for CD206 (M2 marker) (p<.05; n=4) compared to control animals. Whereas L‐CIT+LPS treated animals had increased expression of CD206 (M2 marker) (p<.05; n=4) and lower expression of Arg2 (M1 marker) (p<.001; n=4) compared to control animals. Conclusion In BPD pathogenesis, there is a major shift towards M1 polarization due to the presence of pro‐inflammatory stimuli in the microenvironment, leading to arrested lung development. Our preliminary findings support a role for L‐CIT in regulating macrophage polarization, favoring an anti‐inflammatory M2 phenotype in the presence of inflammatory injury. This further suggests that L‐CIT, a safe nutritional supplement, could reduce inflammatory lung injury during early development.
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Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| Bibliométrie | 0,001 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,002 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».