RGD Reference Report - The sickle cell mouse lung: proinflammatory and primed for allergic inflammation. - Rat Genome Database

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The sickle cell mouse lung: proinflammatory and primed for allergic inflammation.

Authors: Andemariam, B  Adami, AJ  Singh, A  McNamara, JT  Secor, ER  Guernsey, LA  Thrall, RS 
Citation: Andemariam B, etal., Transl Res. 2015 Sep;166(3):254-68. doi: 10.1016/j.trsl.2015.03.001. Epub 2015 Mar 16.
RGD ID: 11354938
Pubmed: PMID:25843670   (View Abstract at PubMed)
PMCID: PMC4537824   (View Article at PubMed Central)
DOI: DOI:10.1016/j.trsl.2015.03.001   (Journal Full-text)

Comorbid asthma in sickle cell disease (SCD) confers higher rates of vaso-occlusive pain and mortality, yet the physiological link between these two distinct diseases remains puzzling. We used a mouse model of SCD to study pulmonary immunology and physiology before and after the induction of allergic airway disease (AAD). SCD mice were sensitized with ovalbumin (OVA) and aluminum hydroxide by the intraperitoneal route followed by daily, nose-only OVA-aerosol challenge to induce AAD. The lungs of naive SCD mice showed signs of inflammatory and immune processes: (1) histologic and cytochemical evidence of airway inflammation compared with naive wild-type mice; (2) bronchoalveolar lavage (BAL) fluid contained increased total lymphocytes, %CD8+ T cells, granulocyte-colony stimulating factor, interleukin 5 (IL-5), IL-7, and chemokine (C-X-C motif) ligand (CXCL)1; and (3) lung tissue and hilar lymph node (HLN) had increased CD4+, CD8+, and regulatory T (Treg) cells. Furthermore, SCD mice at AAD demonstrated significant changes compared with the naive state: (1) BAL fluid with increased %CD4+ T cells and Treg cells, lower %CD8+ T cells, and decreased interferon gamma, CXCL10, chemokine (C-C motif) ligand 2, and IL-17; (2) serum with increased OVA-specific immunoglobulin E, IL-6, and IL-13, and decreased IL-1alpha and CXCL10; (3) no increase in Treg cells in the lung tissue or HLN; and (4) hyporesponsiveness to methacholine challenge. In conclusion, SCD mice have an altered immunologic pulmonary milieu and physiological responsiveness. These findings suggest that the clinical phenotype of AAD in SCD mice differs from that of wild-type mice and that individuals with SCD may also have a unique, divergent phenotype perhaps amenable to a different therapeutic approach.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
IL5Humansickle cell anemia  ISOIl5 (Mus musculus)protein:increased expression:respiratory system fluid/secretionRGD 
Il5Ratsickle cell anemia  ISOIl5 (Mus musculus)protein:increased expression:respiratory system fluid/secretionRGD 
Il5Mousesickle cell anemia  IEP protein:increased expression:respiratory system fluid/secretionRGD 

Objects Annotated

Genes (Rattus norvegicus)
Il5  (interleukin 5)

Genes (Mus musculus)
Il5  (interleukin 5)

Genes (Homo sapiens)
IL5  (interleukin 5)


Additional Information