Do native and polymeric alpha1-antitrypsin activate human neutrophils in vitro?

Area of Science:

• Immunology
• Pulmonology
• Biochemistry

Background:

• Alpha-1 antitrypsin (AAT) Z deficiency is a risk factor for COPD.
• AAT-Z polymers are thought to be pro-inflammatory, but this is debated.
• Previous studies show conflicting results regarding AAT's inflammatory role.

Purpose of the Study:

• To re-examine the effects of AAT on inflammation.
• To investigate the role of endotoxin contamination in AAT's inflammatory activity.

Main Methods:

• In vitro evaluation of native and polymerized AAT-M and AAT-Z.
• Assessing human neutrophil chemotaxis and IL-8 release.
• Varying endotoxin contamination levels (0.08 to 2.55 EU/mg protein).

Main Results:

• Low endotoxin AAT (<0.08 EU/mg) did not stimulate neutrophil chemotaxis or IL-8 release.
• High endotoxin AAT (>0.88 EU/mg) induced neutrophil chemotaxis and IL-8 release.
• Pure AAT inhibited zymosan-induced IL-8 release, while contaminated AAT induced it.

Conclusions:

• The pro-inflammatory effects of AAT are dependent on the presence of other activators.
• Pure AAT preparations demonstrate predominantly anti-inflammatory activity.
• Endotoxin contamination is a critical factor in AAT's observed inflammatory effects.