Endothelin-1 Stimulates Monocytesin vitroto ReleaseChemotactic Activity Identified as Interleukin-8 and Monocyte Chemotactic Protein-1

[摘要] In the present study we examined whether endothelin-1 stimulation ofhuman monocytes causes release of chemotactic factors. It was foundthat monocytes released neutrophil- and monocyte-chemotacticactivity in a dose- and time-dependent manner in response to ET-1.ET-1 did not show any chemotactic activity by itself. NCA wasdetected in monocyte supernatants in response to ET-1(0.01–100 nM) after 1, 4, 8 and 24 h stimulation. MCA wasdetected only after 24 h stimulation with ET-1 (0.1–100 nM).Preincubation of the monocyte cultures with the lipoxygenaseinhibitors nordihydroguaiaretic acid (10−4M) ordiethylcarbamazine (10−9M) completely abolishedthe 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. Amonoclonal antibody against human monocyte chemotactic protein-1neutralized MCA by > 80%. It is concluded that ET-1stimulation of monocytesin vitrocauses release ofneutrophil- and monocyte-chemotactic activity identified as IL-8 andMCP-I respectively. An intact lipoxygenase pathway is crucial forthis effect of ET-1 to occur.

[学科分类] 生理学与病理学