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Activated neutrophils secrete stored alpha 1-antitrypsin
P Pääkkö1, M Kirby, R M du Bois
1Department of Pathology, University of Oulu, Finland.
American Journal of Respiratory and Critical Care Medicine
|December 1, 1996
Summary
Neutrophils store and release alpha-1-antitrypsin (alpha 1-AT) along with neutrophil elastase (NE). This suggests neutrophils possess an intrinsic mechanism to regulate NE activity, maintaining tissue homeostasis.
Area of Science:
- Immunology
- Cell Biology
- Protease Inhibition
Background:
- Neutrophil elastase (NE) is a key protease released by neutrophils.
- Alpha-1-antitrypsin (alpha 1-AT) is the primary inhibitor of NE.
- The role of neutrophils in storing and releasing alpha 1-AT was previously unclear.
Purpose of the Study:
- To investigate whether neutrophils store alpha-1-antitrypsin (alpha 1-AT) for release with neutrophil elastase (NE).
- To determine if neutrophils synthesize and secrete alpha 1-AT in response to activation.
- To explore the implications for local protease regulation.
Main Methods:
- Immunofluorescence and flow cytometry to quantify intracellular alpha 1-AT in neutrophils and monocytes.
- [35S]methionine labeling and immunoprecipitation to assess alpha 1-AT synthesis and secretion.
- Stimulation of neutrophils with cytochalasin B and fMLP to mimic activation.
Main Results:
- Neutrophils contain significantly higher intracellular alpha 1-AT levels than monocytes.
- Neutrophils synthesize a greater proportion of alpha 1-AT compared to monocytes.
- Neutrophil stimulation led to decreased intracellular alpha 1-AT and increased secretion, forming complexes with NE.
Conclusions:
- Neutrophils store and release alpha 1-AT concurrently with NE upon activation.
- This coordinated release suggests an endogenous mechanism for controlling NE activity.
- Neutrophils play a critical role in local protease balance and tissue protection.