Human monocyte adhesion is modulated by endothelin B receptor-coupled nitric oxide release.
Human monocytes have the capacity to produce both endothelin 1 (ET-1) and nitric oxide (NO), yet the roles of these mediators in monocyte function remain unclear. The relationship of ET-1 and NO release to monocyte adhesion was explored using peripheral blood monocytes (PBM) and the human monocytic cell lines THP-1 and U937. Specific binding of 125I-labeled ET-1 to THP-1 was abrogated by pretreatment with the endothelin B (ET(B)) receptor antagonist, BQ-788, but not by the endothelin A (ET(A)) receptor antagonist, BQ-123, consistent with predominant ET(B) receptor expression. Direct measurement of NO with an amperometric probe demonstrated the production of nanomolar concentrations of NO by PBM and THP-1 cells upon treatment with ET-1, which was abrogated by BQ-788, but not BQ-123, pretreatment, suggesting functional coupling of ET(B) receptors to NO release. Indeed, the presence of ET(B) receptor mRNA transcripts was detected in THP-1 and is consistent with previous reports that have demonstrated functional coupling of ET(B) receptors to constitutive NO synthase activation. In contrast, U937 cells did not release NO in response to ET-1 treatment, and mRNA transcripts were not detected in these cells, consistent their failure to bind 125I-labeled ET-1, as previously determined. Exposure of PBM to ET-1 markedly reduced the adhesion of these cells to human saphenous vein, whereas PBM adhesion in the presence of BQ-788 was restored to control levels. These data demonstrate that PBM interactions with the vascular wall can be reduced by autocrine production of NO and suggest that ET(B) receptors may attenuate monocyte activity at sites of inflammation.
King
J M
JM
Department of Biology, Queens College and Graduate School of the City University of New York, Flushing 11367, USA.
Srivastava
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KD
Stefano
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GB
Bilfinger
T V
TV
Bahou
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Magazine
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HI
D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D019332:Endothelin-1 / Q000096:biosynthesis / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000502:physiology*; D012501:Saphenous Vein / Q000166:cytology / Q000378:metabolism
D019332:Endothelin-1; D012333:RNA, Messenger; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; D009569:Nitric Oxide