RGD Reference Report - A role for macrophage migration inhibitory factor in the neonatal respiratory distress syndrome. - Rat Genome Database

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A role for macrophage migration inhibitory factor in the neonatal respiratory distress syndrome.

Authors: Kevill, KA  Bhandari, V  Kettunen, M  Leng, L  Fan, J  Mizue, Y  Dzuira, JD  Reyes-Mugica, M  McDonald, CL  Baugh, JA  O'Connor, CL  Aghai, ZH  Donnelly, SC  Bazzy-Asaad, A  Bucala, RJ 
Citation: Kevill KA, etal., J Immunol. 2008 Jan 1;180(1):601-8.
RGD ID: 4891007
Pubmed: PMID:18097062   (View Abstract at PubMed)

Using a mouse model of neonatal respiratory distress syndrome (RDS), we demonstrate a central role for macrophage migration inhibitory factor (MIF) in lung maturation at the developmental stage when human neonates are most susceptible to RDS. We prematurely delivered mouse pups at embryonic day 18, during the early saccular stage of pulmonary development. Only 8% of the prematurely delivered pups genetically deficient in MIF survived 8 h vs 75% of wild-type controls (p<0.001). This phenotype was corrected when pups of all genotypes were bred from dams heterozygote for MIF deficiency. Local production of MIF in the lung increased at embryonic day 18, continued until full-term at embryonic day 19.5, and decreased in adulthood, thus coinciding with this developmental window. The lungs of pups genetically deficient in MIF were less mature upon histological evaluation, and demonstrated lower levels of vascular endothelial growth factor and corticosterone--two factors that promote fetal lung maturation. In vitro studies support a role for MIF in surfactant production by pulmonary epithelial cells. In a cohort of human neonates with RDS, higher intrapulmonary MIF levels were associated with a lower likelihood of developing bronchopulmonary dysplasia, a sequelae of RDS (p<0.03). This study demonstrates for the first time a role for MIF in lung maturation, and supports a protective role for MIF in newborn lung disease.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
bronchopulmonary dysplasia  IEP 4891007associated with Respiratory Distress Syndrome more ...RGD 
bronchopulmonary dysplasia  ISOMIF (Homo sapiens)4891007; 4891007associated with Respiratory Distress Syndrome more ...RGD 
newborn respiratory distress syndrome  ISOMif (Mus musculus)4891007; 4891007 RGD 
newborn respiratory distress syndrome  IMP 4891007 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Mif  (macrophage migration inhibitory factor)

Genes (Mus musculus)
Mif  (macrophage migration inhibitory factor (glycosylation-inhibiting factor))

Genes (Homo sapiens)
MIF  (macrophage migration inhibitory factor)


Additional Information