Endothelin‐1 Stimulates Monocytes in vitro to ReleaseChemotactic Activity Identified as Interleukin‐8 and Monocyte Chemotactic Protein‐1

• Published in: Mediators of inflammation Vol. 3; no. 2; pp. 155 - 160
• Main Authors: Helset, E., Sildnes, T., Konopski, Z. S.
• Format: Journal Article
• Language: English; Japanese
• Published: 01.01.1994
• ISSN: 0962-9351; 1466-1861
• DOI: 10.1155/S0962935194000207

In the present study we examined whether endothelin‐1 stimulation of human monocytes causes release of chemotactic factors. It was found that monocytes released neutrophil‐ and monocyte‐chemotactic activity in a dose‐ and time‐dependent manner in response to ET‐1. ET‐1 did not show any chemotactic activity by itself. NCA was detected in monocyte supernatants in response to ET‐1 (0.01–100 nM) after 1, 4, 8 and 24 h stimulation. MCA was detected only after 24 h stimulation with ET‐1 (0.1–100 nM). Preincubation of the monocyte cultures with the lipoxygenase inhibitors nordihydroguaiaretic acid (10 −4 M) or diethylcarbamazine (10 −9 M) completely abolished the appearance of NCA and MCA. NCA was neutralized by > 75% using a polyclonal antibody against human interleuktn‐8. The ET‐1 induced release of IL‐8 was confirmed by IL‐8 ELISA. A monoclonal antibody against human monocyte chemotactic protein‐1 neutralized MCA by > 80%. It is concluded that ET‐1 stimulation of monocytes in vitro causes release of neutrophil‐ and monocyte‐chemotactic activity identified as IL‐8 and MCP‐I respectively. An intact lipoxygenase pathway is crucial for this effect of ET‐1 to occur.