ENDOTOXIN INDUCES ORGAN-SPECIFIC ENDOTHELIAL-CELL INJURY

Endothelial cell (EC) injury is observed in clinically important patho logical processes, including bacterial endotoxemia. We hypothesized th at such pathological processes may exhibit target organ heterogeneity due to organ-specific heterogeneity of endothelial cells. To test this hypothesis, endothelial cells of aorta (AO), pulmonary artery (PA), l eft ventricle (LV), and right ventricle (RV) were cultured from indivi dual sheep and exposed to bacterial endotoxin. Marked heterogeneity in endotoxin-induced cytotoxicity was observed. AOEC were the most sensi tive, followed by PAEC, LVEC, and RVEC. This cytotoxicity was manifest ed as programmed cell death (apoptosis). All cells were able to expres s both interleukin-6 and endothelin-1 (ET-1) transcripts. Following ex posure to bacterial endotoxin, interleukin-6 transcripts accumulated i n all cells, whereas ET-1 expression was constant or slightly decrease d. These data suggest that organ-specific heterogeneity of EC responsi veness to endotoxin is a potential determinant of organ-specific resis tance to endotoxin and other mediators of injury.