Dimeric Chemotactic Peptides Discriminate between Chemotaxis and Superoxide Production of Human Neutrophils

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A series of dimeric fMLPs were synthesized by cross-linking with hydrophilic linkers, mono-, di-, tri-, and tetraethylene glycols. All of the dimers showed higher activities than monomeric fMLP in chemotaxis assays for human neutrophils. The magnitude of the activity enhancement was dependent on the linker length. On the other hand, production of superoxide anion was not as enhanced as chemotaxis. The experimental results indicate that these dimers, especially the triethylene glycol-bridged fMLP dimer, D-fMLP-G3, are selective agonists for chemotaxis. In order to distinguish between biological activities and intracellular signaling, rapid mobilization of the intracellular calcium was also measured. D-fMLP-G3 strongly enhanced the calcium mobilization. These results suggest that chemotaxis was correlated with the increase of the intracellular calcium concentration, whereas NADPH oxidase was not activated to generate superoxide by this elevation of cytoplasmic calcium caused by the dimeric ligand, D-fMLP-G3. The dimeric fMLPs might act as useful ligands for studying the intracellular signaling mechanisms of human neutrophils.

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