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Free Radic Biol Med. 2002 Dec 15;33(12):1703-13.

Inhibition of human surfactant protein A function by oxidation intermediates of nitrite.

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  • 1Department of Anesthesiology, University of Alabama at Birmingham, Birmingham, AL 35205-3703, USA.


NitraNitration of protein tyrosine residues by peroxynitrite (ONOO - ) has been implicated in a variety of inflammatory diseases such as acute respiratory distress syndrome (ARDS). Pulmonary surfactant protein A (SP-A) has multiple functions including host defense. We report here that a mixture of hypochlorous acid (HOCl) and nitrite (NO 2 - ) induces nitration, oxidation, and chlorination of tyrosine residues in human SP-A and inhibits SP-A's ability to aggregate lipids and bind mannose. Nitration and oxidation of SP-A was not altered by the presence of lipids, suggesting that proteins are preferred targets in lipid-rich mixtures such as pulmonary surfactant. Moreover, both horseradish peroxidase and myeloperoxidase (MPO) can utilize NO 2 - and hydrogen peroxide (H 2 O 2 ) as substrates to catalyze tyrosine nitration in SP-A and inhibit its lipid aggregation function. SP-A nitration and oxidation by MPO is markedly enhanced in the presence of physiological concentrations of Cl - and the lipid aggregation function of SP-A is completely abolished. Collectively, our results suggest that MPO released by activated neutrophils during inflammation utilizes physiological or pathological levels of NO 2 - to nitrate proteins, and may provide an additional mechanism in addition to ONOO - formation, for tissue injury in ARDS and other inflammatory diseases associated with upregulated *NO and oxidant production.

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