Functional expression of the novel C5a receptor C5L2 in human mast cells (P6014)
Bibliographic record
Abstract
Abstract C5a regulates immune responses by chemoattracting and activating immune cells, i.e. mast cells (MC). Its postulated that C5a regulates MC function by activating a G protein-coupled receptor (GPCR), however it can bind to C5aR, classical GPCR, or C5L2, not G protein coupled, and thought to activate distinct signaling. The presence and role of C5L2 in MC remain unknown. We hypothesized that human MC express functional C5L2. C5aR and C5L2 expression was analyzed by qPCR and flow cytometry. Degranulation, cytokine/chemokine production, adhesion, and migration were measured using standard assays. Lentivirus short hairpin (sh)RNA was utilized to create a stable C5L2-deficient (LAD2-C5L2ko) and a control MC cell line (LAD2-cntr). LAD2 expressed cell-surface C5L2 but not C5aR. C5a stimulated LAD2 degranulation (25%), TNF (22±1.3pg/ml), GM-CSF (15±0.4pg/ml), MCP1 (53±3.6pg/ml) and IP-10 (32±4.3pg/ml) production, adherence to fibronectin (466±92%), and chemotaxis (148.93±0.94%). Pre-treatment with pertussis toxin, wortmanin, U-73122, and Ro-31-8220 inhibited adhesion. Exposure to C5a reduced cell-surface C5L2 expression by ~45%. LAD2-C5L2ko showed decreased expression of GM-CSF and MIP-1β compared to LAD2-cntr. LAD2-C5L2ko showed reduced adhesion and chemotaxis compared to LAD2-cntr. Therefore, we demonstrated that C5a activates LAD2 through C5L2 which is sensitive to G protein signaling inhibitors and provide the first evidence of the crucial role of C5L2 in regulating MC functions.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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.
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; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".