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

Y Sato, JC Hogg, D English… - American journal of …, 2000 - atsjournals.org
Y Sato, JC Hogg, D English, SF van Eeden
American journal of respiratory cell and molecular biology, 2000atsjournals.org
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 (⩾ 10− 8 M) rapidly increased PMN F-actin content (10− 7 M: 58±6%
increase, P< 0.01), whereas lower concentration of ET-1 (⩽ 10− 9 M) caused a small but
consistent decrease in F-actin content (10− 10 M: 6.9±1.5% decrease, P< 0.01) …
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 ( ⩾ 10 8 M) rapidly increased PMN F-actin content (10 7 M: 58 ± 6% increase, P < 0.01), whereas lower concentration of ET-1 ( ⩽ 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 N ω -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.
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