IMMUNOTARGETING OF CATALASE TO ACE OR ICAM-1 PROTECTS PERFUSED RAT LUNGS AGAINST OXIDATIVE STRESS

The pulmonary endothelium is susceptible to oxidative insults. Catalas e conjugated with monoclonal antibodies (MAbs) against endothelial sur face antigens, angiotensin-converting enzyme (MAb 9B9) or intercellula r adhesion molecule-1 (MAb 1A29), accumulates in the lungs after syste mic 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 def ense by these antibody-catalase conjugates in isolated rat lungs perfu sed for 1 h with catalase conjugated with either MAb 9B9, MAb 1A29, or control mouse IgG. Approximately 20% of the injected dose of Ab-I-125 -catalase accumulated in the perfused rat lungs (vs. <5% for IgG-I-125 -catalase). After elimination of nonbound material, the lungs were per fused further for 1 h with 5 mM hydrogen peroxide (H2O2) H2O2 induced an elevation in tracheal and pulmonary arterial pressures (126 +/- 7 a nd 132 +/- 5%, respectively, of the control level), lung wet-to-dry we ight ratio (7.1 +/- 0.4 vs. 6.0 +/- 0.01 in the control lungs), and AC E release into the perfusate (436 +/- 20 vs. 75 +/- 7 mU in the contro l perfusates). Both MAb SBS-catalase and MAb 1A29-catalase significant ly attenuated the H2O2-induced elevation in 1) angiotensin-converting enzyme release to the perfusate (215 +/- 14 and 217 +/- 38 mU, respect ively), 2) lung wet-to-dry ratio (6.25 +/- 0.1 and 6.3 +/- 0.3, respec tively), 3) tracheal pressure (94 +/- 4 and 101 +/- 4%, respectively, of the control level), and 4) pulmonary arterial pressure (103 +/- 3 a nd 104 +/- 7%, respectively, of the control level). Nonconjugated cata lase, nonconjugated antibodies, nonspecific IgG, and IgG-catalase conj ugate 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.