RGD Reference Report - Neutrophil histamine contributes to inflammation in mycoplasma pneumonia. - Rat Genome Database

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Neutrophil histamine contributes to inflammation in mycoplasma pneumonia.

Authors: Xu, X  Zhang, D  Zhang, H  Wolters, PJ  Killeen, NP  Sullivan, BM  Locksley, RM  Lowell, CA  Caughey, GH 
Citation: Xu X, etal., J Exp Med. 2006 Dec 25;203(13):2907-17. Epub 2006 Dec 11.
RGD ID: 5143920
Pubmed: PMID:17158962   (View Abstract at PubMed)
PMCID: PMC2118183   (View Article at PubMed Central)
DOI: DOI:10.1084/jem.20061232   (Journal Full-text)

Mycoplasmas cause chronic inflammation and are implicated in asthma. Mast cells defend against mycoplasma infection and worsen allergic inflammation, which is mediated partly by histamine. To address the hypothesis that mycoplasma provokes histamine release, we exposed mice to Mycoplasma pulmonis, comparing responses in wild-type and mast cell-deficient KitW-sh/KitW-sh (W-sh) mice. Low histamine levels in uninfected W-sh mice confirmed the conventional wisdom that mast cells are principal sources of airway and serum histamine. Although mycoplasma did not release histamine acutely in wild-type airways, levels rose up to 50-fold above baseline 1 week after infection in mice heavily burdened with neutrophils. Surprisingly, histamine levels also rose profoundly in infected W-sh lungs, increasing in parallel with neutrophils and declining with neutrophil depletion. Furthermore, neutrophils from infected airway were highly enriched in histamine compared with naive neutrophils. In vitro, mycoplasma directly stimulated histamine production by naive neutrophils and strongly upregulated mRNA encoding histidine decarboxylase, the rate-limiting enzyme in histamine synthesis. In vivo, treatment with antihistamines pyrilamine or cimetidine decreased lung weight and severity of pneumonia and tracheobronchitis in infected W-sh mice. These findings suggest that neutrophils, provoked by mycoplasma, greatly expand their capacity to synthesize histamine, thereby contributing to lung and airway inflammation.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Mycoplasma pneumoniae pneumonia  ISOHdc (Mus musculus)5143920; 5143920 RGD 
Mycoplasma pneumoniae pneumonia  IEP 5143920 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Hdc  (histidine decarboxylase)

Genes (Mus musculus)
Hdc  (histidine decarboxylase)

Genes (Homo sapiens)
HDC  (histidine decarboxylase)


Additional Information