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

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

The TNF Receptors p55 and p75 Mediate Chemotaxis of PMN Induced by TNFα and a TNFα 36–62 Peptide

The present study was performed to examine whether residues 36–62 of TNFα contain the chemotactic domain of TNFα, and whether the p55 and p75 TNF receptors are involved in TNFα induced chemotaxis. The chemotactic effect of TNFα on PMN was inhibited by the mAbs Hrt-7b and Utr-1, against the p55 and p75 TNF receptors, respectively. Both receptors may therefore be required for mediating the chemotactic effect of TNFcz. The synthetic TNFα 36–62, similar to TNFα, had chemotactic effects on both PMN and monocytes. The chemotactic activity of the TNFα 36–62 peptide on PMN, was inhibited by Htr-7b, Utr-1 and soluble p55 receptor, which shows that the peptide possessed the ability to induce chemotaxis through the TNF receptors. In contrast to TNFα, the peptide did not show a cytotoxic activity against WEHI 164 flbrosarcoma cells. It is suggested that different domains of the TNFα molecule induce distinct biological effects