Thrombin Receptor Activation Inhibits Monocyte Spreading by Induction of ETB Receptor-Coupled Nitric Oxide Release

• Published in: The Journal of immunology (1950) Vol. 161; no. 9; pp. 5039 - 5044
• Main Authors: Srivastava, Kamal D, Magazine, Harold I
• Format: Journal Article
• Language: English
• Published: Am Assoc Immnol 01.11.1998
• DOI: 10.4049/jimmunol.161.9.5039
• ISSN: 0022-1767

Abstract The effect of thrombin receptor activation on monocyte conformation was evaluated using the human monocyte cell line, THP-1, and the thrombin mimetic peptide, Trap-14. Treatment of THP-1 cells with Trap-14 induced rapid rounding of ameboid cells adherent to fibronectin-coated slides, whereas cell rounding was abrogated in the presence of the nitric oxide synthase inhibitor, NG-nitro-l-arginine or the endothelin B receptor antagonist, BQ-788. Endothelin-1 (ET-1) levels in the culture supernatant increased markedly within minutes of Trap-14 exposure with a concomitant loss in cellular ET-1 immunoreactivity. Importantly, loss of ET-1 immunoreactivity was blocked by pretreatment with the vesicle translocation inhibitor, nocodazole. Trap-14 potently induced the release of NO from THP-1 cells, whereas NO release was ablated by preincubation with BQ-788. These data demonstrate that thrombin receptor activation may inhibit cellular spreading as a result of autocrine ET-1 release and subsequent endothelin B receptor-dependent NO production, and suggest that initial exposure of inflammatory cells to thrombin may limit cellular activation and recruitment.