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

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

Abstract (inglese)

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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Tipo di EPrint:Articolo di periodico (online)
Anno di Pubblicazione:2005
Parole chiave (italiano / inglese):antitrypsin, inactivation experiments, pulmonary emphysema
Settori scientifico-disciplinari MIUR:Area 06 - Scienze mediche > MED/10 Malattie dell'apparato respiratorio
Struttura di riferimento:Dipartimenti > Dipartimento di Scienze Mediche e Chirurgiche
Dipartimenti > Dipartimento di Scienze Farmaceutiche
Codice ID:1219
Depositato il:09 Dic 2008
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