Erythropoietin inhibits respiratory epithelial cell apoptosis in a model of ALI

¹ Providence Healthcare Heart + Lung Institute, St. Paul Hospital, University of British Columbia, Vancouver, British Columbia, Canada

^* To whom correspondence should be addressed. E-mail: rmacredmond{at}mrl.ubc.ca.

	Abstract

Fas-mediated apoptosis of the alveolar epithelium is important in the pathogenesis of ARDS. Erythropoietin has cytoprotective properties in other organ systems, and is relatively deficient in critical illness. This study investigates a potential role for erythropoietin in reducing apoptosis in a model of acute lung injury.

Apoptosis was induced in A549 or NHBE cells by Fas activation with CH-11 Fas-cross-linking antibody or by co-culture with peripheral blood neutrophils in a transwell system. The effect of rhEPO on apoptosis was measured by PARP-cleavage and Cell Death Detection Assay. Specific EPO-EPOR mediated effect was determined using EPO-blocking antibody or EPOR siRNA.

Expression of EPOR was demonstrated in A549, NHBE and normal human alveolar epithelium. Fas- and neutrophil-mediated apoptosis of A549 and NHBE cells was inhibited by rhEPO by specific EPO-EPOR mediated mechanism. This anti-apoptotic effect was associated with induction of a pro-apoptotic Bcl-xL/Bax ratio.

Erythropoietin has cytoprotective properties in respiratory epithelium in an in vitro model which may indicate a potential therapeutic role in acute lung injury.