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1 Institute for Environmental Medicine and 4 Department of Pharmacology, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6068; 2 Departments of Anesthesiology and Pharmacology, University of Illinois at Chicago, Chicago, Illinois 60612; and 3 Department of Physiology and Biophysics, Louisiana State University Medical Center, Shreveport, Louisiana 39532
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.
endothelium; hydrogen peroxide; angiotensin-converting enzyme; intercellular adhesion molecule-1
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