Dysregulated neutrophil function in individuals with alpha-1 antitrypsin deficiency caused by modified membrane cholesterol content.

Bakr Jundi,Noreen Lacey,Noel G Mcelvaney,Michelle White,Emer Reeves

doi:10.1186/1753-6561-9-s7-a7

Bakr Jundi, Noreen Lacey + Show 3 more

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https://doi.org/10.1186/1753-6561-9-s7-a7

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Journal: BMC Proceedings	Publication Date: Oct 27, 2015
License type: cc-by

Affiliation: Beaumont Hospital

Abstract

Background Individuals with alpha-1 antitrypsin (AAT) deficiency (AATD) are predisposed to early-onset emphysema and neutrophils are the primary effector cells responsible for the pathological manifestations of AATD lung disease. As AAT interacts directly with the circulating neutrophil membrane [1], the question that this project addressed was: are AATD neutrophils structurally and functionally altered? The aim of this study was to explore a link between disrupted membrane structure and impaired trafficking of cholesterol in AATD neutrophils.

Highlights

Individuals with alpha-1 antitrypsin (AAT) deficiency (AATD) are predisposed to early-onset emphysema and neutrophils are the primary effector cells responsible for the pathological manifestations of AATD lung disease
Dysregulated neutrophil function in individuals with alpha-1 antitrypsin deficiency caused by modified membrane cholesterol content
In summary, our findings have demonstrated for the first time increased calcium, increased calpain activity causing proteolytic cleavage of caveolin-1, and decreased membrane cholesterol content of AATD neutrophils

Summary

Introduction

Individuals with alpha-1 antitrypsin (AAT) deficiency (AATD) are predisposed to early-onset emphysema and neutrophils are the primary effector cells responsible for the pathological manifestations of AATD lung disease. As AAT interacts directly with the circulating neutrophil membrane [1], the question that this project addressed was: are AATD neutrophils structurally and functionally altered? The aim of this study was to explore a link between disrupted membrane structure and impaired trafficking of cholesterol in AATD neutrophils As AAT interacts directly with the circulating neutrophil membrane [1], the question that this project addressed was: are AATD neutrophils structurally and functionally altered? The aim of this study was to explore a link between disrupted membrane structure and impaired trafficking of cholesterol in AATD neutrophils

Objectives

Results

Conclusion