Title

Subtle Differences between Human and Rabbit Neutrophil Receptors Shown by the Secretagogue Activity of Constrained Formyl Peptides

Document Type

Article

Language

eng

Publication Date

1-15-1997

Publisher

Elsevier

Source Publication

Archives of Biochemistry and Biophysics

Source ISSN

0003-9861

Abstract

Stereochemically constrained extended β-antiparallel and folded β-turn analogs of the chemotactic agentN-formyl-Met-Leu-Phe-OH were tested for their ability to induce the release of β-glucuronidase from human and rabbit neutrophils. Selected biologically active peptides were further examined for their capacity to inhibit the binding of f-Met-Leu-[3H]Phe to whole human neutrophils at 4°C. The results suggest that Dpg2analogs with the extended backbone are significantly more potent in human peripheral blood neutrophils than the folded β-turn analogs. Surprisingly, in rabbit peritoneal neutrophils, the extended Dpg2analog appears to be marginally less active than the flexible parent peptide and the folded Ac6c2analog. In human neutrophils, the secretagogue activity increases in the following order with alteration in the C-terminal functions: -CONH2< -COOMe < -COOH << -COOBzl. However, this order of potency differs from that observed for the rabbit formyl peptide receptor (-COOH < -COOMe < -CONH2<< -COOBzl). In human neutrophils, the peptides’ ability to compete for the receptor binding site of f-Met-Leu-[3H]Phe correlates well with their secretagogue potency. The results provide convincing evidence for the existence of subtle differences between human peripheral blood neutrophils and rabbit peritoneal neutrophils with regard to ligand–receptor interactions of constrained chemotactic peptides. What is new and novel in this report is that constrained peptides can distinguish between the rabbit and human chemotactic peptide receptors which have so far been believed to have similar response to secretagogue agents. The data emphasize that directly relating the secretagogue activity observed in rabbit neutrophils to that observed in human neutrophils may not be unequivocal.

Comments

Archives of Biochemistry and Biophysics, Vol. 337, No. 2 (January 15, 1997): 267-274. DOI.

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