A peptide with unique receptor specificity - Stimulation of phosphoinositide hydrolysis and induction of superoxide generation in human neutrophils
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- Title
- A peptide with unique receptor specificity - Stimulation of phosphoinositide hydrolysis and induction of superoxide generation in human neutrophils
- Authors
- Seo, JK; Choi, SY; Kim, Y; Baek, SH; Kim, KT; Chae, CB; Lambeth, JD; Suh, PG; Ryu, SH
- Date Issued
- 1997-02-15
- Publisher
- AMER ASSOC IMMUNOLOGISTS
- Abstract
- Previously, we identified peptides that stimulate phosphoinositide hydrolysis in several leukocyte cell lines from mixtures of random hexapeptide sequences. Moreover, the peptides activate phospholipase C via a pertusis toxin-sensitive C protein-coupled receptor. We now investigate the structure-activity relationship of the peptides with the goal of improving the activity of the peptides, as well as the biologic function of the peptides. Substitution of the L-methionine at the C terminus of peptides with D-methionine markedly increased the effectiveness of the peptides. The half-maximal effective concentrations of MKYMPm-NH2 and WKYMVm-NH2 for stimulation of phosphoinositide hydrolysis in U266 cells were 30 and 0.5 nM, respectively. By BIAcore analysis we confirmed the existence of a receptor for WKYMVm-NH2. Furthermore, the intracellular calcium concentration increase induced by WKYMVm-NH2 was not inhibited by several chemoattractants (FMLP, IL-8, platelet-activating factor, C5a, granulocyte-macrophage CSF, and granulocyte CSF) suggests that WKYMVm-NH2 has a unique cell surface receptor on leukocytes. WKYMVm-NH2 stimulated the phosphoinositide hydrolysis in U937, HL60, and U266 cells, as well as in human neutrophils. Moreover, WKYMVm-NH2 is more effective than FMLP in the production of superoxide in human neutrophils. The data suggest that WKYMVm-NH2 may have the ability to activate the microbicidal functions of human neutrophils.
- Keywords
- BETA-GAMMA-SUBUNITS; PHOSPHOLIPASE-C; CELL-LINE; PHOSPHATIDYLINOSITOL 3-KINASE; INTRACELLULAR CALCIUM; SIGNAL-TRANSDUCTION; BOVINE BRAIN; HL-60 CELLS; SUBSTANCE-P; ACTIVATION
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/21384
- ISSN
- 0022-1767
- Article Type
- Article
- Citation
- JOURNAL OF IMMUNOLOGY, vol. 158, no. 4, page. 1895 - 1901, 1997-02-15
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