Alpha-1-antitrypsin is present in the specific granules of human eosinophilic granulocytes

Background Eosinophils may be found at sites of inflammation, for example in asthma, allergy and helminthic infestation, but their role in human inflammatory disease is unclear. Objective In the present study, we investigated the presence of alpha-1-antitrypsin (AAT), a serine proteinase inhibitor, in human eosinophils. Methods and results When lysates of highly purified eosinophils were subjected to Western blotting, with a chemiluminescent substrate, immunoreactive bands were seen. An ELISA was developed to measure the AAT content, which was found to be about 100 ng/5 x 10(6) eosinophils, about 50 ng/5 x 10(6) neutrophils, and about 25 ng/5 x 10(6) monocytes. Immunoelectron microscopy showed localization of AAT to the specific granules of eosinophils. During prolonged incubation of eosinophils, no significant increase in the total amount of AAT could be detected by ELISA. However, there was an increased level of AAT in the medium, in parallel with a decrease in the intracellular AAT content, suggesting release of preformed AAT. Apparent complex formation between iodinated elastase and AAT in eosinophil lysates provided evidence that the AAT is functionally active. Conclusion On the basis of these findings it is suggested that by releasing AAT, eosinophils may, in a microenvironment, play a role in counteracting the tissue damage caused by serine proteinases released by neutrophils in inflammatory conditions.