Proficient versus deficient primary human hepatocytes.

<p>RT-PCR <b>e</b>xpression of several genes showed no remarkable difference between proficient and deficient primary human hepatocytes. SERPINA1 expression was at equal levels in both deficient and proficient hepatocytes, Ki67 levels differed between the groups, although this was not significant. However, expression of CASP3 was increased in A1AT deficient hepatocytes (Mann-Whitney <i>U</i> test) * P<0.05, ns not significant.</p

Characteristics of liver tissues used for cell isolation.

<p>Characteristics of liver tissues used for cell isolation.</p

Purified A1AT reduces SERPINA1 expression in a dose-dependent manner in primary human hepatocytes.

<p>(<b>A</b>) Exogenously added purified A1AT reduced SERPINA1 expression in primary human hepatocytes isolated from both proficient and deficient liver tissue. The reduction was more prominent following Oncostatin M (10ng/ml) stimulation (Kruskal-Wallis test on ranks). SERPINA1 gene expression was reduced in a dose-dependent manner with marked decrease at A1AT levels of >1 mg/ml (<b>B</b>) Oncostatin M showed increased expression of SERPINA1 in primary human hepatocytes (Mann-Whitney <i>U</i> test), * P<0.05, ** P <.001, *** P<0.001, **** P<0.0001).</p

Effect of purified A1AT therapy on SERPINA1 gene expression in the PiZZ lung.

<p>SERPINA1 gene expression in lung tissue from PiZZ patients receiving purified A1AT (Prolastin) therapy (n = 10) compared to PiZZ patients without therapy (n = 4) showed similar tendencies to other cell types investigated. There might be reduced SERPINA1 expression in treated PiZZ patients, the difference did however not reach statistical significance (P = 0.0539, Mann-Whitney <i>U</i> test).</p

Purified A1AT reduces SERPINA1 expression in adherent PBMCs <i>in vitro</i>.

<p>Adherent PBMCs isolated from healthy donors showed a reduction in SERPINA1 expression following purified A1AT protein treatment. The reduction could be observed in both naïve and LPS-stimulated cells and was in coherence with the effects seen in hepatocytes (n = 7, Wilcoxon test), * P<0.05.</p

Increased rate of proliferation in the PiZZ liver.

<p>Liver tissue from PiZZ patients (n = 6) was stained for proliferation using Ki67 antibody and visualized by diaminobenzidine. Liver tissue from A1AT proficient individuals (n = 13) was used as reference. PiZZ livers show increased frequency of Ki67 positive (proliferating) cells compared to the proficient group. No differences could be observed in the non-parenchymal cells (NPC). (Mann-Whitney <i>U</i> test) * P<0.05, ns not significant. Scale bars: 100μm.</p