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Submitted on August 22, 2002
Accepted on November 1, 2002
Evidence for Antibody-Catalyzed Ozone Formation in Bacterial Killing and Inflammation
Paul Wentworth Jr. 1,Jonathan E. McDunn 1,Anita D. Wentworth 1,Cindy Takeuchi 2,Jorge Nieva 3,Teresa Jones 1,Cristina Bautista 1,Julie M. Ruedi 3,Abel Gutierrez 3,Kim D. Janda 1,Bernard M. Babior 3,Albert Eschenmoser 4,Richard A. Lerner 1
1 Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. 2 Department of Immunology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. 3 Department of Molecular and Experimental Medicine and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. 4 Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA; Laboratorium fuer organische Chemie, ETH Zuerich, Universitaetstr. 16 CH-8092 Zuerich, Switzerland.
Recently we discovered that antibodies catalyze the generationof hydrogen peroxide (H2O2) from singlet molecular oxygen (1O2*)and water. Here we show this process can lead to efficient killingof bacteria, regardless of the antigen specificity of the antibody.H2O2 production by antibodies was not alone sufficient for bacterialkilling and further studies suggested that the antibody-catalyzedwater-oxidation pathway produced an additional molecular specieswith a chemical signature similar to that of ozone. This speciesis also generated during the oxidative burst of activated humanneutrophils and during inflammation. These observations suggestthat alternative pathways may exist for biological killing ofbacteria that are mediated by potent oxidants new to biology.
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