Tytuł:

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

Autor:

Surmiak, Marcin

Temat i słowa kluczowe:

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

Abstrakt:

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.

Miejsce wydania:

Kraków

Stopień studiów:

2 - studia doktoranckie

Dyscyplina:

biologia molekularna ; immunologia

Instytucja nadająca tytuł:

Wydział Lekarski

Promotor:

Sanak, Marek

Data:

2014

Data wydania:

2014

Typ:

Praca doktorska

Sygnatura:

ZB-120299

Język:

pol

Prawa dostępu:

nieograniczony