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Title: Influence of alpha-1 antitrypsin on anti–proteinase 3 antibodies mediated neutrophil activation, in vitro model

Abstract:

Classical pathway of cANCA (IgG anti-PR3) neutrophil activation assumes that both fragments of IgG, Fab and Fc are required to complete granulocyte activation. These processes can be regulated be alpha-1 antitrypsin (A1AT). The aim of this study was to analyze molecular mechanisms of cANCA mediated neutrophil activation and evaluation how different types of A1AT can affect these processes. Reactive oxygen species generation was observed only in granulocytes stimulated with native cANCAs. Analysis of neutrophils’ gene expression profile showed detectable levels of mRNA expressed by 126 out of 152 genes. In cells stimulated with native cANCAs up-regulation in mRNA expression was observed only in 13 genes (CACNA1D, CACNB2,VCAM1, PDE4C, PLA2G4C, PLCB4, PTGDR, CCL2, CXCL2, MMP9, IRAK1, RAC1, RHA; p<0,05) and in case of granulocytes stimulated with F(ab)2 fragments of cANCAs' up-regulation of 17 genes was observed (PLA2G7, PTGDR, PTGER3, IL1R1, IL1RL1, RAC1, MAPK1, MAPK8, NR3C1, DNAJB1, CYSLTR1, HPGD, CD302, F2R, F2RL1, IER3, RPL41; p<0,05). Experiments with A1AT showed that the native form of this protein can inhibit PR3/cANCA complex formation, as well as cANCA mediated neutrophil genes activation and ROS production. Furthermore, higher concentration of NE/A1AT complexes was observed in supernatants from cells prestimulated with native A1AT.

Place of publishing:

Kraków

Level of degree:

2 - studia doktoranckie

Degree discipline:

biologia molekularna ; immunologia

Degree grantor:

Uniwersytet Jagielloński. Collegium Medicum. Wydział Lekarski.

Promoter:

Jacek Musiał

Date issued:

2013

Format:

application/pdf

Identifier:

oai:dl.cm-uj.krakow.pl:3665

Call number:

ZB-120299

ControlNumberVIRTUA:

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Language:

pol

Access rights:

tylko w bibliotece

Location of original object:

Biblioteka Medyczna Uniwersytetu Jagiellońskiego- Collegium Medicum

Object collections:

Last modified:

Jun 26, 2019

In our library since:

Mar 18, 2014

Number of object content hits:

4

Number of object content views in PDF format

4

All available object's versions:

http://dl.cm-uj.krakow.pl:8080/publication/3665

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ZB-120299 Jun 26, 2019
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