Type

Journal Article

Authors

Noel G McElvaney
Sean Fitzgerald
Ramia Jameel
Rebecca Wolfe
Killian Hurley
Emer P Reeves
David A Bergin

Subjects

Microbiology

Topics
immunology female signal transduction cell degranulation autoimmunity neutrophils lactoferrin blood male tumor necrosis factor alpha young adult medicine and health sciences autoantibodies middle aged adult humans physiology cytology adolescent alpha 1 antitrypsin

The circulating proteinase inhibitor α-1 antitrypsin regulates neutrophil degranulation and autoimmunity. (2014)

Abstract Pathological inflammation and autoimmune disease frequently involve elevated neutrophil activity in the absence of infectious agents. Tumor necrosis factor-α (TNF-α) contributes to many of the problems associated with autoimmune diseases. We investigated the ability of serum α-1 antitrypsin (AAT) to control TNF-α biosynthesis and signaling in neutrophils and assessed whether AAT deficiency (AATD) is a TNF-α-related disease. In vitro studies demonstrate that serum AAT coordinates TNF-α intracellular signaling and neutrophil degranulation of tertiary and secondary granules via modulation of ligand-receptor interactions. AATD patients homozygous for the Z allele were characterized by increased activation of the TNF-α system, as demonstrated by increased membrane TNF-α levels and increased plasma concentrations of TNF receptor 1 and neutrophil-released secondary and tertiary granule proteins. The incidence of autoantibodies directed against degranulated lactoferrin and surface protein accessible to these antibodies was increased in ZZ-AATD, leading to an enhanced rate of neutrophil reactive oxygen species production. Treatment of ZZ-AATD individuals with AAT augmentation therapy resulted in decreased membrane TNF-α expression and plasma levels of granule antigenic proteins and immunoglobulin G class autoantibodies. These results provide a mechanism by which AAT augmentation therapy affects TNF-α signaling in the circulating neutrophil, indicating promising potential of this therapy for other TNF-α-related diseases.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed
Ireland -> Royal College of Surgeons in Ireland -> Medicine Articles
Ireland -> Royal College of Surgeons in Ireland -> RCSI Undergraduate Research
Ireland -> Royal College of Surgeons in Ireland -> Department of Medicine
Ireland -> Royal College of Surgeons in Ireland -> RCSI Undergraduate Research Articles

Full list of authors on original publication

Noel G McElvaney, Sean Fitzgerald, Ramia Jameel, Rebecca Wolfe, Killian Hurley, Emer P Reeves, David A Bergin

Experts in our system

1
Noel G McElvaney
Royal College of Surgeons in Ireland
Total Publications: 194
 
2
Emer P Reeves
Royal College of Surgeons in Ireland
Total Publications: 63
 
3
David A Bergin
Royal College of Surgeons in Ireland
Total Publications: 28