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

Marina Gorrini, Anna Lupi, Paolo Iadarola, Conceição Dos Santos, Paola Rognoni, Daniele Dalzoppo, Natalia Carrabino, Ernesto Pozzi, Aldo Baritussio, Maurizio Luisetti

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Abstract

Background. α1-antitrypsin and surfactant protein-A (SP-A) are major lung defense proteins. With the hypothesis that SP-A could bind α1-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 α1-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 α1-antitrypsin for neutrophil elastase. The findings were similar when SP-A was coupled with the Z variant of α1-antitrypsin. The carbohydrate recognition domain of SP-A appeared to be a major determinant of the interaction, by recognizing α1-antitrypsin carbohydrate chains. However, binding of SP-A carbohydrate chains to the α1-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 α1-antitrypsin. Conclusions. We conclude that the binding of SP-A to α1-antitrypsin results in a decrease of the inhibition of neutrophil elastase. This interaction could have potential implications in the physiologic regulation of α1-antitrypsin activity, in the pathogenesis of pulmonary emphysema, and in the defense against infectious agents.

Original languageEnglish
Article number146
JournalRespiratory Research
Volume6
DOIs
Publication statusPublished - Dec 13 2005

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ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Medicine(all)

Cite this

Gorrini, M., Lupi, A., Iadarola, P., Dos Santos, C., Rognoni, P., Dalzoppo, D., Carrabino, N., Pozzi, E., Baritussio, A., & Luisetti, M. (2005). SP-A binds alpha1-antitrypsin in vitro and reduces the association rate constant for neutrophil elastase. Respiratory Research, 6, [146]. https://doi.org/10.1186/1465-9921-6-146