Purinergic P2X<sub>7</sub> receptor function in lung alveolar macrophages: Pharmacologic characterization and bidirectional regulation by Th1 and Th2 cytokines
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
Abstract Purinergic P2X 7 receptors have been shown in the lung, but little is known concerning P2X 7 function in pulmonary macrophages. In this study we characterized P2X 7 ‐dependent responses to extracellular ATP in resident and activated alveolar macrophages (AM) obtained by bronchoalveolar lavage of rats. Incubation of AM with high concentrations of ATP (5mM) or 3′‐O‐(4‐benzoyl)benzoyl‐ATP (B z ATP) (0.5mM), a P2X 7 agonist, induced: 1) rapid pore formation, 2) apoptosis, and 3) enhanced release of IL‐1α, IL‐1β, and IL‐6, but not TNF‐α following priming with lipopolysaccharide (LPS). Furthermore, higher expression of P2X 7 receptor in AM was associated with increased formation of Type 2 multinucleated giant cells (Type 2 MGC) in response to GMCSF. Immunopharmacological analysis also showed that P2X 7 ‐dependent pore formation in AM was significantly increased by LPS (1 µg/ml) and the T helper 1 (Th1) cytokines, interferon‐γ (100U/ml), and, to a lesser extent, TNF‐α (>20 ng/ml). In contrast, the T helper 2 (Th2) cytokines IL‐4 (1pg/ml) as well as IL‐10 (1ng/ml) significantly inhibited these P2X 7 receptor functions. Transforming growth factor‐β (TGF‐β), a known deactivator of macrophages, had no significant effect. Our results demonstrate that AM exhibit all the characteristics of a functional P2X 7 receptor which upon appropriate stimulation activates the proinflammatory IL‐1→IL‐6 cytokine cascade and the formation of MGC, a hallmark of granulomatous reactions. Moreover, Th1 and Th2 cytokines reciprocally regulate P2X 7 function, suggesting a role for P2X 7 in pulmonary diseases associated with chronic inflammatory responses. Drug Dev. Res. 59:118–127, 2003. © 2003 Wiley‐Liss, Inc.
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.
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it