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Respir Res. 2005 Dec 13;6:146.

SP-A binds alpha1-antitrypsin in vitro and reduces the association rate constant for neutrophil elastase.

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  • 1Laboratorio di Biochimica e Genetica, Clinica di Malattie dell'Apparato Respiratorio, IRCCS Policlinico San Matteo, Università di Pavia, Pavia, Italy. m.gorrini@smatteo.pv.it

Abstract

BACKGROUND:

Alpha1-antitrypsin and surfactant protein-A (SP-A) are major lung defense proteins. With the hypothesis that SP-A could bind alpha1-antitrypsin, we designed a series of in vitro experiments aimed at investigating the nature and consequences of such an interaction.

METHODS AND RESULTS:

At an alpha1-antitrypsin:SP-A molar ratio of 1:1, the interaction resulted in a calcium-dependent decrease of 84.6% in the association rate constant of alpha1-antitrypsin for neutrophil elastase. The findings were similar when SP-A was coupled with the Z variant of alpha1-antitrypsin. The carbohydrate recognition domain of SP-A appeared to be a major determinant of the interaction, by recognizing alpha1-antitrypsin carbohydrate chains. However, binding of SP-A carbohydrate chains to the alpha1-antitrypsin amino acid backbone and interaction between carbohydrates of both proteins are also possible. Gel filtration chromatography and turnover per inactivation experiments indicated that one part of SP-A binds several molar parts of alpha1-antitrypsin.

CONCLUSION:

We conclude that the binding of SP-A to alpha1-antitrypsin results in a decrease of the inhibition of neutrophil elastase. This interaction could have potential implications in the physiologic regulation of alpha1-antitrypsin activity, in the pathogenesis of pulmonary emphysema, and in the defense against infectious agents.

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