Inhibition of intracellular signaling pathways.

<p>NK cells from six controls were cultured with K562 and PMA-I alone (control) or in the presence of the inhibitor drugs LY294002 (25 µM), PD98059 (25 µM), Rapamycin (100 nM) and Rottlerin (5 µM). NK cell function was assessed for CD107a expression (A) and IFN-γ production (B) in response to addition of inhibitor drugs in culture. CD107a expression is shown to be reduced by addition of inhibitor drugs affecting pathways of cellular activation. Statistical significance was defined as <i>p</i>&lt;0.05. Graphed data presented as mean ± SEM.</p

NK cell and T cell IFN-γ production in the presence of immunosuppressive drugs.

<p>PBMC from 20 healthy controls were stimulated in culture with the cell line K562 or PMA-I in the presence of varying concentrations of immunosuppressive drugs. NK cell IFN-γ production measured in response to stimulation with K562 cell line (A) and PMA-I (B). T cell IFN-γ production measured in response to PMA-I stimulation (C). Statistical significance was defined as <i>p</i>&lt;0.001. Graphed data are presented as mean ± SEM. Symbols represent immunosuppressive drugs: •, Cyclosporine A; □, MPA; ▴, Prednisolone. Shaded areas signify therapeutic range.</p

Lung transplant patient and healthy control demographics.

<p>Tx indicates transplant; D indicates donor; R indicates recipient; CF indicates cystic fibrosis; EMP indicates emphysema; COPD indicates chronic obstructive pulmonary disease; BRON indicates bronchiectasis; <i>NA</i> indicates not applicable.</p>*<p>Patients who received Anti-thymocyte globulin.</p

Proliferation of NK cells in the presence of immunosuppressive drugs.

<p>MACS enriched NK cells from three healthy controls were labelled with CFSE and stimulated in culture for three days with a combination of IL-2, IL-12 and 721.221 cell lines in the presence or absence of immunosuppressants Cyclosporine A, MPA and Prednisolone. An example of the change in CFSE intensity as the cells proliferate is shown (A). NK cell proliferation is displayed in response to treatment with varying concentrations of the immunosuppressive drugs (B, <i>p</i>&lt;0.05 for all). Graphed data are presented as the mean ± SEM from three independent experiments. Symbols represent immunosuppressive drugs: •, Cyclosporine A; □, MPA; ▴, Prednisolone. Shaded area signifies therapeutic range.</p

NK cell and T cell cytotoxicity in the presence of immunosuppressive drugs.

<p>PBMC from 20 healthy controls were stimulated in culture with the cell line K562 or PMA-I in the presence or absence of varying concentrations of immunosuppressive drugs. An example of the flow cytometry gating strategy for identification of positive expression is shown (A). NK cell cytotoxicity measured by CD107a surface expression (B) and chromium release assay, at a 50∶1 effector-to-target ratio (C), in response to K562 stimulation. CD107a expression for whole CD56+ NK cells (D), T cells (E) and NK cell subsets CD56bright and CD56dim (F) measured following PMA-I stimulation. Statistical significance was defined as <i>p</i>&lt;0.001. Graphed data are presented as mean ± SEM. Symbols represent immunosuppressive drugs: •, dashed bars: Cyclosporine A; □, white bars: MPA; ▴, grey bars: Prednisolone. Shaded areas signify therapeutic range.</p

Functional changes in NK cells from lung transplant patients.

<p>PBMC from ten LTR, not receiving immunosuppression pre-transplant (Pre-Tx), were stimulated in culture with PMA-I. Individual graphs of NK cell CD107a expression (closed square) and IFN-γ production (open circle) from LTR with clinically stable post-transplantation follow-up (Tx #6, #7, #9), episodes of acute rejection (Tx #2, #3, #4) or viral infection (Tx #1, #5, #8, #10). The arrows represent the occurrence of each clinical event in the months post-transplant.</p

Summary of patient and donor characteristics stratified by ischemic conditioning or sham treatment.

<p>Summary of patient and donor characteristics stratified by ischemic conditioning or sham treatment.</p

Correlations between activins and follistatin.

<p>Correlations between activins and follistatin.</p

Substantial Increases Occur in Serum Activins and Follistatin during Lung Transplantation - Fig 1

<p><b>(A)</b> Serum activin A levels for the patients are illustrated and compared to the upper and lower reference thresholds for normal healthy volunteers (25). <b>(B)</b> Serum activin B levels for the patients are illustrated and compared to the upper and lower reference thresholds for normal healthy volunteers (25). <b>(C)</b> Serum follistatin levels for the patients are illustrated and compared to the upper and lower reference thresholds for normal healthy volunteers (25). <b>(D)</b> Serum Activin A to follistatin ratios for the patients are compared with the upper and lower reference ratio thresholds for normal healthy volunteers (25). <b>(E)</b> Serum Activin B to follistatin ratios for the patients are compared with the upper and lower reference ratios for normal healthy volunteers (25).</p

Correlations between activin to follistatin ratios, and other cytokines, and between other cytokines.

<p>Correlations between activin to follistatin ratios, and other cytokines, and between other cytokines.</p