ORIGINAL ARTICLE: LPS‐Induced Murine Abortions Require C5 but not C3, and are Prevented by Upregulating Expression of the CD200 Tolerance Signaling Molecule
Bibliographic record
Abstract
PROBLEM: Lipopolysaccharide (LPS) acts via tlr4 to promote Th1 cytokine secretion and abortions. LPS is an essential co-factor in spontaneous abortion in the CBA x DBA/2 model and in stress-triggered abortions. In the CBA x DBA/2 model, C3a, C5a, and fgl2 prothrombinase participate in triggering inflammation that terminates embryo viability. As fgl2 prothrombinase (via thrombin) can generate C5a, it was predicted that LPS-driven abortions (which require fgl2) would be independent of C3. CD200Fc can prevent abortions in the CBA x DBA/2 model, but an action through Fc could not be excluded. METHOD OF STUDY: C3(-/-) and C5(-/-) knock-out mice on a B6 background were syngeneically mated and Salmonella enteritidis LPS was administered i.p. on day 6.5 or pregnancy along with 2 mg progesterone in sesame oil s.c. The total number of implants and the number of resorbing embryos were counted on day 13.5 of pregnancy. CD200-rtTA double transgenic homozygous males (B6 background) mated with B6(+/+) females were similarly treated. To up-regulate CD200 expression in embryonic trophoblasts, doxycycline was added to the drinking water from the time of mating. RESULTS: The LPS boosted the abortion rate from 15.5% (control) to 42.0% in C3(-/-) mice (chi(2) = 9.28, P < 0.005). In C5(-/-) mice, there was no increase in abortion rate with LPS compared to progesterone-treated controls (22.8%versus 26.3%, P = NS). LPS-treated transgenic mice given LPS + progesterone had a 42.5% abortion rate, but when the mice were given doxycycline to induce expression of CD200 by the embryo, the abortion rate was only 8.3% (chi(2) = 14.40, P < 0.005, Fisher's exact test P = 0.00007). CONCLUSION: C5, but not C3, appears necessary for LPS-driven abortions. Up-regulation of CD200 can prevent LPS-driven abortions, possibly by altering dendritic cells to promote Treg cell development or by a direct suppressive action on macrophages and mast cells that also express CD200 receptors.
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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) | 0.001 | 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 | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.006 | 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".