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Gorrini, Marina and Lupi, Anna and Iadarola, Paolo and Dos Santos, Conceição and Rognoni, Paola and Dalzoppo, Daniele and Carrabino, Natalia and Pozzi, Ernesto and Baritussio, Aldo and Luisetti, Maurizio (2005) SP-A binds alpha1-antitrypsin in vitro and reduces the association rate constant for neutrophil elastase. [Online journal papers]

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Per gentile concessione di: http://respiratory-research.com/content/6/1/146

Abstract (english)

Background

?1-antitrypsin and surfactant protein-A (SP-A) are major lung defense proteins. With the hypothesis that SP-A could bind ?1-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 ?1-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 ?1-antitrypsin for neutrophil elastase. The findings were similar when SP-A was coupled with the Z variant of ?1-antitrypsin. The carbohydrate recognition domain of SP-A appeared to be a major determinant of the interaction, by recognizing ?1-antitrypsin carbohydrate chains. However, binding of SP-A carbohydrate chains to the ?1-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 ?1-antitrypsin.

Conclusion

We conclude that the binding of SP-A to ?1-antitrypsin results in a decrease of the inhibition of neutrophil elastase. This interaction could have potential implications in the physiologic regulation of ?1-antitrypsin activity, in the pathogenesis of pulmonary emphysema, and in the defense against infectious agents.


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EPrint type:Online journal papers
Anno di Pubblicazione:2005
Key Words:antitrypsin, inactivation experiments, pulmonary emphysema
Settori scientifico-disciplinari MIUR:Area 06 - Scienze mediche > MED/10 Malattie dell'apparato respiratorio
Struttura di riferimento:Dipartimenti > pre 2012 - Dipartimento di Scienze Mediche e Chirurgiche
Dipartimenti > pre 2012 - Dipartimento di Scienze Farmaceutiche
Codice ID:1219
Depositato il:09 Dec 2008
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