期刊
JOURNAL OF IMMUNOLOGY
卷 180, 期 1, 页码 601-608出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.180.1.601
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- EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT [K12HD043494] Funding Source: NIH RePORTER
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [K08HL074195] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI042310] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES [R01AR050498] Funding Source: NIH RePORTER
- NHLBI NIH HHS [K08 HL074195, HL5041, HL07778] Funding Source: Medline
- NIAID NIH HHS [1R01-AI042310] Funding Source: Medline
- NIAMS NIH HHS [1R01-AR050498] Funding Source: Medline
- NICHD NIH HHS [K12 HD043494] Funding Source: Medline
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.
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