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Fibronectin receptor of human macrophages recognizes the sequence Arg-Gly-Asp-Ser
Abstract:
When cultured human monocytes (MO) were spread on fibronectin (Fn)-coated surfaces, C3 receptors on the MO exhibited markedly enhanced capacity to promote phagocytosis. The activation of C3 receptors by Fn was mediated by a receptor that recognizes a sequence, Arg-Gly-Asp-Ser (RGDS), present in the cell-binding domain of Fn. Soluble, RGDS-containing peptides inhibited the activation of C3 receptors caused by surface-bound Fn, and surface-bound, RGDS-containing peptides themselves caused activation of the C3 receptors of attached MO. Although soluble, RGDS-containing peptides bound to Fn receptors, such monovalent ligation was insufficient to activate C3 receptors.
Insights
Fibronectin (Fn) enhances monocyte (MO) phagocytosis by activating C3 receptors via the Arg-Gly-Asp-Ser (RGDS) sequence. Surface-bound RGDS peptides activate C3 receptors, while soluble peptides do not, indicating multivalent binding is key.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Monocytes (MO) play a crucial role in the immune system, including phagocytosis.
- Fibronectin (Fn) is an extracellular matrix protein involved in cell adhesion and signaling.
- C3 receptors on monocytes are critical for immune responses.
Purpose of the Study:
- To investigate the mechanism by which fibronectin (Fn) enhances monocyte (MO) phagocytosis.
- To identify the specific molecular interactions mediating Fn-induced C3 receptor activation.
Main Methods:
- Cultured human monocytes (MO) were cultured on fibronectin (Fn)-coated surfaces.
- The role of the Arg-Gly-Asp-Ser (RGDS) sequence in Fn-mediated activation was assessed using soluble and surface-bound RGDS peptides.
- Phagocytic capacity and C3 receptor activation were measured.
Main Results:
- Fibronectin (Fn) coating significantly enhanced the phagocytic capacity of monocytes (MO) via C3 receptor activation.
- The Arg-Gly-Asp-Ser (RGDS) sequence within Fn mediates this activation.
- Surface-bound RGDS peptides induced C3 receptor activation, whereas soluble RGDS peptides did not, suggesting multivalent binding is required.
Conclusions:
- Fibronectin (Fn) binding to monocytes (MO) activates C3 receptors, enhancing phagocytosis.
- The Arg-Gly-Asp-Ser (RGDS) sequence is essential for this activation.
- Multivalent engagement of Fn receptors by surface-bound RGDS is necessary for C3 receptor activation.