The seven-transmembrane receptor, C5L2, is a stimulatory receptor on human mast cells
Bibliographic record
Abstract
Complement anaphylatoxin 5a (C5a) is a powerful inflammatory mediator involved in the pathology of inflammatory diseases such as chronic idiopathic urticaria. C5a binds to two receptors, C5aR, a G protein-coupled receptor, and C5L2, a 7-transmembrane receptor deficient in G protein coupling. The role of C5L2 in human mast cells (huMC) is unknown. We hypothesized that huMC express C5aR and/or C5L2 and C5a activates huMC to produce pro-inflammatory mediators through one or both of these receptors. C5aR and C5L2 expression on the huMC line, LAD2, was analyzed by quantitative PCR and flow cytometry. Degranulation was measured by β-hexosaminidase assay. Eicosanoids and cytokines/chemokines production was measured by ELISA and cytometric bead array. C5L2 expression was knocked-out using C5L2 shRNA lentiviral particles (LvP) and a stably C5L2 cell line was selected for further analysis of C5L2 function. LAD2 expressed mRNA for C5aR and C5L2. However, flow cytometry analysis showed that LAD2 expressed surface C5L2 but not C5aR. C5a stimulated LAD2 to produce TNF (22±1.3pg/ml), GM-CSF (15±0.4pg/ml), MCP-1 (53±3.6pg/ml) and IP-10 (32±4.3pg/ml). C5a failed to degranulate LAD2 and generate eicosanoids. C5L2 shRNA LvP completely knocked-out C5L2 expression. C5L2-depleted LAD2 did not respond to C5a while control shRNA-treated LAD2 did. LAD2 express C5L2 but not C5aR, and C5a induces production of cytokines/chemokines suggesting that C5L2 is an excitatory receptor in huMC. Knock-down of C5L2 abrogates C5a function. This is the first study to demonstrate a functional role of C5L2 in huMC. The observation that C5L2, not C5aR, may be more important in complement-mediated activation of huMC may provide novel insights into treatment of complement-mediated inflammation.
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How this classification was reachedexpand
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) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.008 | 0.002 |
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 itClassification
machine, unvalidatedMachine predicted; both teacher heads agree on what is shown here.
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".