RGD Reference Report - Influence of DMT1 and iron status on inflammatory responses in the lung. - Rat Genome Database

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Influence of DMT1 and iron status on inflammatory responses in the lung.

Authors: Kim, J  Molina, RM  Donaghey, TC  Buckett, PD  Brain, JD  Wessling-Resnick, M 
Citation: Kim J, etal., Am J Physiol Lung Cell Mol Physiol. 2011 Apr;300(4):L659-65. Epub 2011 Jan 28.
RGD ID: 5688709
Pubmed: PMID:21278260   (View Abstract at PubMed)
PMCID: PMC3075097   (View Article at PubMed Central)
DOI: DOI:10.1152/ajplung.00343.2010   (Journal Full-text)

Divalent metal transporter 1 (DMT1) is the major iron transporter responsible for duodenal dietary iron absorption and is required for erythropoiesis. Recent studies suggest that loss of DMT1 activity could be involved in metal-related lung injury, but little is known about the effects of iron status and DMT1 function on pulmonary inflammation. To better define the role of DMT1 and iron status in pulmonary inflammatory responses, we performed bronchoalveolar lavage (BAL) following intratracheal instillation of lipopolysaccharide (LPS) to the Belgrade rat, an animal model deficient in DMT1 function. In the basal state, the BAL fluid of Belgrade rats had more macrophages and higher lactate dehydrogenase, myeloperoxidase, albumin, and hemoglobin levels compared with heterozygote control rats. Following LPS instillation, the macrophage fraction relative to total BAL cell content and levels of albumin and IgM were increased in Belgrade rats compared with controls. In contrast, heterozygote Belgrade rats made anemic by diet-induced iron deficiency exhibited attenuated inflammatory responses to LPS. These combined results show that pulmonary inflammation can be modified by both DMT1 and iron status. Loss of DMT1 alters pulmonary responses necessary for lung homeostasis in the basal state and enhances LPS-induced inflammation and therefore would contribute to progression of lung injury.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
pneumonia  ISOSlc11a2 (Rattus norvegicus)5688709; 5688709 RGD 
pneumonia  IMP 5688709 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Slc11a2  (solute carrier family 11 member 2)

Genes (Mus musculus)
Slc11a2  (solute carrier family 11 (proton-coupled divalent metal ion transporters), member 2)

Genes (Homo sapiens)
SLC11A2  (solute carrier family 11 member 2)


Additional Information