Am. J. Respir. Cell Mol. Biol., Volume 23, Number 3, September, 2000 404-410

Endothelin-1 Changes Polymorphonuclear Leukocytes' Deformability and CD11b Expression and Promotes Their Retention in the Lung

Yukio Sato, James C. Hogg, Dean English, and Stephan F. van Eeden

University of British Columbia Pulmonary Research Laboratory, St. Paul's Hospital, Vancouver, British Columbia, Canada

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 ( 10⁸ M) rapidly increased PMN F-actin content (10⁷ M: 58 ± 6% increase, P < 0.01), whereas lower concentration of ET-1 ( 10⁹ M) caused a small but consistent decrease in F-actin content (10¹⁰ 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 10⁷ M of ET-1 (P < 0.01), and enhanced the F-actin content decrease by 10¹⁰ M of ET-1 (P < 0.01). Preincubation of PMNs with N-nitro-L-arginine methylester prevented the F-actin content decrease by 10¹⁰ M of ET-1. ET-1 (10⁷ M) reduced the deformability of PMNs (P < 0.01), which was inhibited by preincubation of PMNs with SNP (P < 0.05). ET-1 (10⁹ to 10⁷ 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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