Inducible nitric oxide synthase (iNOS) and regulation of leucocyte/endothelial cell interactions: studies in iNOS‐deficient mice
Bibliographic record
Abstract
It is well established that constitutive production of nitric oxide is central to numerous processes in the microvasculature, including controlling the trafficking of inflammatory leucocytes. However, during many inflammatory responses induction of inducible nitric oxide synthase (iNOS) increases nitric oxide production. The role of iNOS-derived nitric oxide in modulating leucocyte recruitment is less well understood, although recent studies using iNOS-deficient mice have begun to examine this issue. This article describes much of the work that implicates iNOS as having a role in controlling leucocyte recruitment, including the intravital microscopy studies which revealed that iNOS-deficient mice have elevated leucocyte-endothelial cell interactions during endotoxaemia. Furthermore in additional studies, we compared expression of endothelial adhesion molecules in wild-type and iNOS-deficient mice, under conditions in which iNOS was expressed. Adhesion molecule expression was measured using an in vivo dual radiolabel immunoassay. To induce iNOS, mice were treated with either 1 or 50 microg of bacterial lipopolysaccharide (LPS), and 4 h later expression of P-selectin, E-selectin and vascular cell adhesion molecule-1 was determined in eight different tissues. In nearly all cases, adhesion molecule expression did not differ between the two types of mice, either in the absence of an inflammatory stimulus, or following LPS treatment. These findings indicate that iNOS does not regulate expression of endothelial adhesion molecules either under basal conditions, or during the endotoxaemic response. This further suggests that alterations in leucocyte function may mediate the modulating effect of iNOS on leucocyte recruitment.
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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 | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.003 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| 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) | 0.000 | 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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, 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".