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

Autor: E. Helset, T. Sildnes, Z. S. Konopski
Jazyk: angličtina
Rok vydání: 1994
Předmět:
Zdroj: Mediators of Inflammation, Vol 3, Iss 2, Pp 155-160 (1994)
Druh dokumentu: article
ISSN: 0962-9351
1466-1861
09629351
DOI: 10.1155/S0962935194000207
Popis: 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.
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