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.
Sato
Y
Y
University of British Columbia Pulmonary Research Laboratory, St. Paul's Hospital, Vancouver, British Columbia, Canada.
Hogg
J C
JC
English
D
D
van Eeden
S F
SF
D000199:Actins / Q000378:metabolism; D000818:Animals; D001011:Aorta; D002232:Carbocyanines; D048429:Cell Size / Q000187:drug effects / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004912:Erythrocytes / Q000166:cytology; D005260:Female; D005434:Flow Cytometry; D005456:Fluorescent Dyes; D006801:Humans; D008168:Lung / Q000098:blood supply / Q000166:cytology / Q000276:immunology*; D016177:Macrophage-1 Antigen / Q000096:biosynthesis*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009504:Neutrophils / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D011652:Pulmonary Circulation / Q000276:immunology; D011817:Rabbits; D014665:Vasodilator Agents / Q000494:pharmacology
D000199:Actins; C101089:CM-DiI; D002232:Carbocyanines; D019332:Endothelin-1; D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D016177:Macrophage-1 Antigen; D014665:Vasodilator Agents; D009599:Nitroprusside; D009569:Nitric Oxide; D019331:NG-Nitroarginine Methyl Ester