Histamine Produced by Gram-Negative Bacteria Impairs Neutrophil’s Antimicrobial Response by Engaging the Histamine 2 Receptor
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Bibliographic record
Abstract
We found that histamine (10<sup>−9</sup> M) did not have any effect on the <i>in vitro</i> capture of <i>Escherichia coli</i> by neutrophils but accelerated its intracellular killing. In contrast, histamine (10<sup>−6</sup> M) delayed the capture of <i>Escherichia coli</i> by neutrophils and reduced the amounts of pHrodo zymosan particles inside acidic mature phagosomes. Histamine acted through the H<sub>4</sub>R and the H<sub>2</sub>R, which are coupled to the Src family tyrosine kinases or the cAMP/protein kinase A pathway, respectively. The protein kinase A inhibitor H-89 abrogated the delay in bacterial capture induced by histamine (10<sup>−6</sup> M) and the Src family tyrosine kinase inhibitor PP2 blocked histamine (10<sup>−9</sup> M) induced acceleration of bacterial intracellular killing and tyrosine phosphorylation of proteins. To investigate the role of histamine in pathogenicity, we designed an <i>Acinetobacter baumannii</i> strain deficient in histamine production (hdc::TOPO). <i>Galleria mellonella</i> larvae inoculated with the wild-type <i>Acinetobacter baumannii</i> ATCC 17978 strain (1.1 × 10<sup>5</sup> CFU) died rapidly (100% death within 40 h) but not when inoculated with the <i>Acinetobacter baumannii</i> hdc::TOPO mutant (10% mortality). The concentration of histamine rose in the larval haemolymph upon inoculation of the wild type but not the <i>Acinetobacter baumannii</i> hdc::TOPO mutant, such concentration of histamine blocks the ability of hemocytes from <i>Galleria mellonella</i> to capture <i>Candida albicans</i> <i>in vitro</i>. Thus, bacteria-producing histamine, by maintaining high levels of histamine, may impair neutrophil phagocytosis by hijacking the H<sub>2</sub>R.
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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 | 0.003 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.002 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 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