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. 2017 May 11;3(6):e159.
doi: 10.1097/TXD.0000000000000676. eCollection 2017 Jun.

Activin Biology After Lung Transplantation

Glen P Westall  1   2 , Gregory I Snell  1   2 , Monika Loskot  1 , Bronwyn Levvey  1   2 , Robyn O'Hehir  1   2 , Mark P Hedger  2   3 , David M de Kretser  2   3
Affiliations

Activin Biology After Lung Transplantation

Glen P Westall et al. Transplant Direct. .

Abstract

Background: Activins A and B, members of the TGF-β superfamily, are produced as part of the physiological response to tissue damage and the resulting proinflammatory response. Given that lung allograft reperfusion results in an inflammatory response, it is likely that the activins and their binding protein follistatin will form part of the regulatory response. There is a need to document the response of these proteins to allograft reperfusion to determine if there is a role for the use of follistatin to control the biological actions of the activins because some of these are potentially damaging.

Methods: Serum from 48 consecutive patients undergoing lung transplantation (LTx) was collected at 2, 6, 12, and 26 weeks post-LTx. The serum levels of activin A and B and follistatin were measured by enzyme-linked immunosorbent assay and specific radioimmunoassays and compared with clinical events.

Results: Serum activin A and B levels were at the upper limit of the normal ranges at 2 weeks post-LTx decreasing thereafter to 12 weeks post-LTx (P < 0.05). In contrast, serum follistatin levels were unchanged between 2 and 12 weeks, with a late significant increase at 24 week post-LTx (P < 0.01). Patients with primary graft dysfunction had lower serum follistatin levels (7.7 vs 9.5 ng/mL; P = 0.04) and a higher activin A/follistatin ratio (13.1 vs 10.4; P = 0.02) at 2 weeks post-LTx.

Conclusions: Activin and follistatin levels vary with time form LTX and reflect a proinflammatory environment. Future studies will elucidate associations with chronic lung allograft dysfunction and the therapeutic potential of exogenous follistatin administration.

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Conflict of interest statement

Conflict of Interest: David de Kretser and Mark Hedger are shareholders in Paranta Biosciences, a company that is developing follistatin as a therapeutic.

Figures

FIGURE 1
FIGURE 1
Longitudinal changes in mean serum levels of (A) activin A, (B) activin B and (C) follistatin measured at 2 weeks (bronchoscopy 1), 6 weeks (bronchoscopy 2), 3 months (bronchoscopy 3) and 6 months (bronchoscopy 4) postlung transplant. Comparative normal values (−−---).
FIGURE 2
FIGURE 2
Longitudinal changes in (A) activin A/follistatin and (B) activin B/follistatin ratio after LTx.
FIGURE 3
FIGURE 3
Longitudinal changes in the levels of serum activin B in lung transplant patients with positive microbiology in the BAL compared with those without positive microbiological isolates.
See this image and copyright information in PMC

References

    1. Snell GI, Paraskeva M, Westall GP. Managing bronchiolitis obliterans syndrome (BOS) and chronic lung allograft dysfunction (CLAD) in children: what does the future hold? Paediatr Drugs. 2013;15:281–289. - PubMed
    1. Thompson BR, Westall GP, Paraskeva M, et al. Lung transplantation in adults and children: putting lung function into perspective. Respirology. 2014;19:1097–1105. - PubMed
    1. Hedger MP, de Kretser DM. The activins and their binding protein, follistatin—diagnostic and therapeutic targets in inflammatory disease and fibrosis. Cytokine Growth Factor Rev. 2013;24:285–295. - PubMed
    1. Winnall WR, Wu H, Sarraj MA, et al. Expression patterns of activin, inhibin and follistatin variants in the adult male mouse reproductive tract suggest important roles in the epididymis and vas deferens. Reprod Fertil Dev. 2013;25:570–580. - PubMed
    1. Wu H, Chen Y, Winnall WR, et al. Regulation of activin A release from murine bone marrow-derived neutrophil precursors by tumour necrosis factor-α and insulin. Cytokine. 2013;61:199–204. - PubMed