Immunotargeting of catalase to ACE or ICAM-1 protects perfused rat lungs against oxidative stress

Elena N. Atochina, Irina V. Balyasnikova, Sergei M. Danilov, D. Neil Granger, Aron B. Fisher, Vladimir R. Muzykantov*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

88 Scopus citations

Abstract

The pulmonary endothelium is susceptible to oxidative insults. Catalase conjugated with monoclonal antibodies (MAbs) against endothelial surface antigens, angiotensin-converting enzyme (MAb 9B9) or intercellular adhesion molecule-1 (MAb 1A29), accumulates in the lungs after systemic injection in rats (V. Muzykantov, E. Atochina, H. Ischiropoulos, S. Danilov, and A. Fisher. Proc. Natl. Acad. Sci. USA 93: 5213-5218, 1996). The present study characterizes the augmentation of antioxidant defense by these antibody- catalase conjugates in isolated rat lungs perfused for 1 h with catalase conjugated with either MAb 9B9, MAb 1A29, or control mouse IgG. Approximately 20% of the injected dose of Ab-125I-catalase accumulated in the perfused rat lungs (vs. <5% for IgG-125I-catalase). After elimination of nonbound material, the lungs were perfused further for 1 h with 5 mM hydrogen peroxide (H2O2). H2O2 induced an elevation in tracheal and pulmonary arterial pressures (126 ± 7 and 132 ± 5%, respectively, of the control level), lung wet-to-dry weight ratio (7.1 ± 0.4 vs. 6.0 ± 0.01 in the control lungs), and ACE release into the perfusate (436 ± 20 vs. 75 ± 7 mU in the control perfusates). Both MAb 9B9-catalase and MAb 1A29-catalase significantly attenuated the H2O2-induced elevation in 1) angiotensin-converting enzyme release to the perfusate (215 ± 14 and 217 ± 38 mU, respectively), 2) lung wet-to-dry ratio (6.25 ± 0.1 and 6.3 ± 0.3, respectively), 3) tracheal pressure (94 ± 4 and 101 ± 4%, respectively, of the control level), and 4) pulmonary arterial pressure (103 ± 3 and 104 ± 7%, respectively, of the control level). Nonconjugated catalase, nonconjugated antibodies, nonspecific IgG, and IgG-catalase conjugate had no protective effect, thus confirming the specificity of the effect of MAb-catalase. These results support a strategy of catalase immunotargeting for protection against pulmonary oxidative injury.

Original languageEnglish (US)
Pages (from-to)L806-L817
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume275
Issue number4 19-4
DOIs
StatePublished - 1998

Keywords

  • Angiotensin-converting enzyme
  • Endothelium
  • Hydrogen peroxide
  • Intercellular adhesion molecule-1

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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