title: A critical regulatory role for macrophage migration inhibitory factor in hyperoxia-induced injury in the developing murine lung.
abstract: BACKGROUND
  The role and mechanism of action of MIF in hyperoxia-induced acute lung injury (HALI) in the newborn lung are not known. We hypothesized that MIF is a critical regulatory molecule in HALI in the developing lung.
  
  
  METHODS
  We studied newborn wild type (WT), MIF knockout (MIFKO), and MIF lung transgenic (MIFTG) mice in room air and hyperoxia exposure for 7 postnatal (PN) days. Lung morphometry was performed and mRNA and protein expression of vascular mediators were analyzed.
  
  
  RESULTS
  MIF mRNA and protein expression were significantly increased in WT lungs at PN7 of hyperoxia exposure. The pattern of expression of Angiopoietin 2 protein (in MIFKO>WT>MIFTG) was similar to the mortality pattern (MIFKO>WT>MIFTG) in hyperoxia at PN7. In room air, MIFKO and MIFTG had modest but significant increases in chord length, compared to WT. This was associated with decreased expression of Angiopoietin 1 and Tie 2 proteins in the MIFKO and MIFTG, as compared to the WT control lungs in room air. However, on hyperoxia exposure, while the chord length was increased from their respective room air controls, there were no differences between the 3 genotypes.
  
  
  CONCLUSIONS
  These data point to the potential roles of Angiopoietins 1, 2 and their receptor Tie2 in the MIF-regulated response in room air and upon hyperoxia exposure in the neonatal lung.
authors: Department of Pediatrics, Yale University, New Haven, Connecticut, United States of America.
authors: Huanxing
authors: H
authors: Sun
authors: Rayman
authors: R
authors: Choo-Wing
authors: Angara
authors: A
authors: Sureshbabu
authors: Juan
authors: J
authors: Fan
authors: Lin
authors: L
authors: Leng
authors: Shuang
authors: S
authors: Yu
authors: Dianhua
authors: D
authors: Jiang
authors: Paul
authors: P
authors: Noble
authors: Robert J
authors: RJ
authors: Homer
authors: Richard
authors: R
authors: Bucala
authors: Vineet
authors: V
authors: Bhandari
mesh_terms: D042682:Angiopoietins / Q000235:genetics; D000818:Animals; D018893:Bronchoalveolar Lavage; D002452:Cell Count; D005786:Gene Expression Regulation; D055786:Gene Knockout Techniques; D018496:Hyperoxia / Q000150:complications*; D015850:Interleukin-6 / Q000378:metabolism; D008168:Lung / Q000254:growth & development* / Q000378:metabolism* / Q000473:pathology; D055370:Lung Injury / Q000209:etiology* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008263:Macrophage Migration-Inhibitory Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype; D042787:Receptor, TIE-2 / Q000235:genetics; D040262:Receptors, Vascular Endothelial Growth Factor / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D042682:Angiopoietins; D015850:Interleukin-6; D008263:Macrophage Migration-Inhibitory Factors; D042461:Vascular Endothelial Growth Factor A; D042787:Receptor, TIE-2; D040262:Receptors, Vascular Endothelial Growth Factor
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