Type

Other / n/a

Authors

Noel G McElvaney
Shane J O'Neill
Patrick Geraghty
Eimear O'Flynn
Osama Kandalaft
Ahmed Aljorfi
Khalifah Alsaleh
Oliver J McElvaney
Kevin Molloy
Kerstin Pohl
and 5 others

Subjects

Pharmacology

Topics
cystic fibrosis cell degranulation inositol 1 recombinant proteins female chronic obstructive pulmonary disease male calcium medicine and health sciences neutrophils cytosol chemotaxis intracellular space 5 trisphosphate inositol 1 4 5 trisphosphate secretory leukocyte peptidase inhibitor pulmonary disease chronic obstructive immunologic factors biological adult models biological humans cytoskeleton oxidation reduction anti inflammatory agents neutrophil activation

Intracellular secretory leukoprotease inhibitor modulates inositol 1,4,5-triphosphate generation and exerts an anti-inflammatory effect on neutrophils of individuals with cystic fibrosis and chronic obstructive pulmonary disease. (2013)

Abstract Secretory leukoprotease inhibitor (SLPI) is an anti-inflammatory protein present in respiratory secretions. Whilst epithelial cell SLPI is extensively studied, neutrophil associated SLPI is poorly characterised. Neutrophil function including chemotaxis and degranulation of proteolytic enzymes involves changes in cytosolic calcium (Ca(2+)) levels which is mediated by production of inositol 1,4,5-triphosphate (IP3) in response to G-protein-coupled receptor (GPCR) stimuli. The aim of this study was to investigate the intracellular function of SLPI and the mechanism-based modulation of neutrophil function by this antiprotease. Neutrophils were isolated from healthy controls (n = 10), individuals with cystic fibrosis (CF) (n = 5) or chronic obstructive pulmonary disease (COPD) (n = 5). Recombinant human SLPI significantly inhibited fMet-Leu-Phe (fMLP) and interleukin(IL)-8 induced neutrophil chemotaxis (P < 0.05) and decreased degranulation of matrix metalloprotease-9 (MMP-9), hCAP-18, and myeloperoxidase (MPO) (P < 0.05). The mechanism of inhibition involved modulation of cytosolic IP3 production and downstream Ca(2+) flux. The described attenuation of Ca(2+) flux was overcome by inclusion of exogenous IP3 in electropermeabilized cells. Inhibition of IP3 generation and Ca(2+) flux by SLPI may represent a novel anti-inflammatory mechanism, thus strengthening the attractiveness of SLPI as a potential therapeutic molecule in inflammatory airway disease associated with excessive neutrophil influx including CF, non-CF bronchiectasis, and COPD.
Collections Ireland -> Royal College of Surgeons in Ireland -> Medicine Articles
Ireland -> Royal College of Surgeons in Ireland -> Department of Medicine

Full list of authors on original publication

Noel G McElvaney, Shane J O'Neill, Patrick Geraghty, Eimear O'Flynn, Osama Kandalaft, Ahmed Aljorfi, Khalifah Alsaleh, Oliver J McElvaney, Kevin Molloy, Kerstin Pohl and 5 others

Experts in our system

1
Noel G McElvaney
Royal College of Surgeons in Ireland
Total Publications: 194
 
2
Shane J O'Neill
Royal College of Surgeons in Ireland
Total Publications: 84
 
3
Patrick Geraghty
Royal College of Surgeons in Ireland
Total Publications: 13
 
4
Oliver J McElvaney
Royal College of Surgeons in Ireland
 
5
Kevin Molloy
Royal College of Surgeons in Ireland
Total Publications: 19
 
6
Kerstin Pohl
Royal College of Surgeons in Ireland