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


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.


CONCLUSIONS
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.
Gorrini
Marina
M
Laboratorio di Biochimica e Genetica, Clinica di Malattie dell'Apparato Respiratorio, IRCCS Policlinico San Matteo, Università di Pavia, Pavia, Italy. m.gorrini@smatteo.pv.it
Lupi
Anna
A
Iadarola
Paolo
P
Dos Santos
Conceição
C
Rognoni
Paola
P
Dalzoppo
Daniele
D
Carrabino
Natalia
N
Pozzi
Ernesto
E
Baritussio
Aldo
A
Luisetti
Maurizio
M
D004789:Enzyme Activation; D007700:Kinetics; D019272:Leukocyte Elastase / Q000737:chemistry*; D011485:Protein Binding; D037662:Pulmonary Surfactant-Associated Protein A / Q000737:chemistry*; D000515:alpha 1-Antitrypsin / Q000737:chemistry*
D037662:Pulmonary Surfactant-Associated Protein A; D000515:alpha 1-Antitrypsin; D019272:Leukocyte Elastase