Endothelin-1 changes polymorphonuclear leukocytes' deformability and CD11b expression and promotes their retention in the lung.

Endothelin (ET)1 influences polymorphonuclear leukocyte (PMN)- endothelial cell interactions. The aim of this study was to examine the effect of ET-1 on factors that influence PMN-endothelial interaction and retention in the lung both in vitro and in vivo. In vitro, high concentration of ET-1 (> or = 10(-8) M) rapidly increased PMN F-actin content (10(-7) M: 58 +/- 6% increase, P<0.01), whereas lower concentration of ET-1 (< or = 10(-9) M) caused a small but consistent decrease in F-actin content (10(-10) M: 6.9+/-1.5% decrease, P< 0.01). Preincubation of PMNs with the nitric oxide donor sodium nitroprusside (SNP) inhibited the F-actin content increase by 10(-7) M of ET-1 (P<0.01), and enhanced the F-actin content decrease by 10(-10) M of ET-1 (P<0.01). Preincubation of PMNs with Nomega-nitro-L-arginine methylester prevented the F-actin content decrease by 10(-10) M of ET-1. ET-1 (10(-7) M) reduced the deformability of PMNs (P<0.01), which was inhibited by preincubation of PMNs with SNP (P<0.05). ET-1 (10(-9) to 10(-7) M) increased CD11b expression of PMNs (P<0.01), which was inhibited by preincubation of PMNs with SNP. In vivo studies showed that the retention of PMNs treated with ET-1 increased from 45+/-8 to 70+/-5% compared with naive PMNs during their first pass through the lung (P<0.05). We conclude that ET-1 changes the F-actin content, the deformability, and the CD11b expression of PMNs in a dose-dependent fashion and that this leads to increased PMN sequestration in pulmonary microvessels.