Title:

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

Author:

Surmiak, Marcin

Subject:

alpha-1 antitrypsin ; cANCA ; proteinase 3 ; neutrophil activation

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:

Wydział Lekarski

Promoter:

Sanak, Marek

Date:

2014

Date issued:

2014

Type:

Praca doktorska

Call number:

ZB-120299

Language:

pol

Access rights:

nieograniczony