Enhancement of ovalbumin-induced pulmonary eosinophilia by intranasal administration of alpha1-proteinase inhibitor type 2 antisense oligonucleotides

Immunol Lett. 2009 Jan 29;122(1):76-83. doi: 10.1016/j.imlet.2008.12.001. Epub 2008 Dec 25.


To identify asthma-susceptibility genes, we did proteome analyses of the lung from control and ovalbumin-sensitized BALB/c mice. Among the 6 up-regulated proteins is alpha(1)-protease inhibitor (alpha(1)-PI) type 2, which is a member of the serine protease inhibitor superfamily of protease inhibitors that participate in a variety of physiological functions, including extracellular matrix remodeling and inflammation. The up-regulated expression of alpha(1)-PI type 2 was confirmed by real-time PCR. Then we examined mRNA expression of five members of the alpha(1)-PI family genes (alpha(1)-PI types 1-5) in several organs of BALB/c mice and found that in addition to the liver, all the organs tested also expressed different isoforms of alpha(1)-PI in a tissue-specific manner, albeit to a lesser extent compared with the liver. When a similar study was performed with C57BL/6 mice, which have been shown to be more susceptible to ovalbumin-induced asthma than BALB/c mice, a pair of remarkable differences between the mouse strains were revealed: (1) the magnitude of alpha(1)-PI type 2 mRNA in all the organs was much higher in BALB/c than in C57BL/6 mice and (2) alpha(1)-PI type 2 is the only isoform expressed in the lung of BALB/c, but not of C57BL/c mice. Using the antisense oligonucleotide technology to specifically down-regulate expression of alpha(1)-PI type 2, we demonstrated that pulmonary infiltration of eosinophils was significantly increased by intranasal administration of alpha(1)-PI type 2 antisense oligonucleotides in OVA-sensitized mice, suggesting that alpha(1)-PI type 2 may suppress the progress of asthma, probably by acting on neutrophil elastase, which can produce many of the pathological features of asthma.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intranasal
  • Animals
  • Cell Movement / genetics*
  • Cell Movement / immunology
  • Eosinophils / immunology
  • Eosinophils / metabolism*
  • Eosinophils / pathology
  • Gene Expression
  • Lung / immunology
  • Lung / metabolism
  • Lung / pathology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Oligonucleotides, Antisense / administration & dosage
  • Oligonucleotides, Antisense / chemistry
  • Oligonucleotides, Antisense / genetics
  • Organ Specificity
  • Ovalbumin / immunology
  • Proteomics
  • Pulmonary Eosinophilia / immunology*
  • Pulmonary Eosinophilia / therapy
  • Species Specificity
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • alpha 1-Antitrypsin / chemistry
  • alpha 1-Antitrypsin / genetics
  • alpha 1-Antitrypsin / immunology
  • alpha 1-Antitrypsin / metabolism*


  • Oligonucleotides, Antisense
  • alpha 1-Antitrypsin
  • Ovalbumin