Volume 9 Supplement 7

Abstracts from the 4th International Conference for Healthcare and Medical Students (ICHAMS) 2014

Open Access

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

  • Bakr Jundi1,
  • Michelle White1,
  • Noreen Lacey1,
  • Noel G McElvaney1 and
  • Emer Reeves1
BMC Proceedings20159(Suppl 7):A7

https://doi.org/10.1186/1753-6561-9-S7-A7

Published: 27 October 2015

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.

Methods

Circulating neutrophils were purified from blood of patients with AATD and from healthy control individuals (n=7). Membranes and cytosols were isolated from neutrophils by sucrose-gradient ultracentrifugation. Cholesterol and calcium levels were fluorometric quantified and calpain levels measured using a calpain activity assay. Caveolin-1 expression was examined by Western blot analysis. Statistical comparisons were performed by Student's t-test.

Results

Neutrophil cytosols of AATD individuals had increased calcium concentrations (n=7, p=0.04) and activation of the calcium dependent protease calpain (n=7, p=0.01). Furthermore, levels of the cholesterol trafficking protein caveolin-1 were significantly lower in AATD neutrophil cytosols (n=6, p=0.01) leading to significantly decreased membrane cholesterol content when compared to healthy control cells (n=5, P=0.045).

Conclusions

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. This novel data may in part explain the dysregulated activity of this innate immune cell in AATD.

Authors’ Affiliations

(1)
Dept. of Medicine, Respiratory Research, Beaumount Hospital

References

  1. Bergin D A, et al: alpha-1 Antitrypsin regulates human neutrophil chemotaxis induced by soluble immune complexes and IL-8. J Clin Invest. 120: 4236-4250.Google Scholar

Copyright

© Jundi et al. 2015

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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