Westall Glen P, Snell Gregory I, Loskot Monika, Levvey Bronwyn, O'Hehir Robyn, Hedger Mark P, de Kretser David M
Allergy, Immunology and Respiratory Medicine, Alfred Hospital, Victoria, Australia.
Department of Medicine, Monash University, Melbourne, Victoria, Australia.
Transplant Direct. 2017 May 11;3(6):e159. doi: 10.1097/TXD.0000000000000676. eCollection 2017 Jun.
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.
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.
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 ( < 0.05). In contrast, serum follistatin levels were unchanged between 2 and 12 weeks, with a late significant increase at 24 week post-LTx ( < 0.01). Patients with primary graft dysfunction had lower serum follistatin levels (7.7 vs 9.5 ng/mL; = 0.04) and a higher activin A/follistatin ratio (13.1 vs 10.4; = 0.02) at 2 weeks post-LTx.
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.
激活素A和B是转化生长因子-β超家族的成员，它们作为对组织损伤及由此产生的促炎反应的生理反应的一部分而产生。鉴于肺移植再灌注会引发炎症反应，激活素及其结合蛋白卵泡抑素很可能是调节反应的一部分。有必要记录这些蛋白质对移植再灌注的反应，以确定使用卵泡抑素控制激活素的生物学作用是否有作用，因为其中一些激活素可能具有潜在损害性。
收集48例连续接受肺移植（LTx）患者在LTx后2、6、12和26周的血清。通过酶联免疫吸附测定和特异性放射免疫测定法测量激活素A和B以及卵泡抑素的血清水平，并与临床事件进行比较。
LTx后2周时血清激活素A和B水平处于正常范围的上限，此后至LTx后12周逐渐下降（P<0.05）。相比之下，血清卵泡抑素水平在2至12周之间无变化，在LTx后24周出现后期显著升高（P<0.01）。原发性移植功能障碍患者在LTx后2周时血清卵泡抑素水平较低（7.7对9.5 ng/mL；P = 0.04），激活素A/卵泡抑素比值较高（13.1对10.4；P = 0.02）。
激活素和卵泡抑素水平随LTx时间而变化，反映了促炎环境。未来的研究将阐明与慢性肺移植功能障碍的关联以及外源性卵泡抑素给药的治疗潜力。
