Activation of kinin B 1 receptors induces chemotaxis of human neutrophils

P. Ehrenfeld, C. Millan, C. E. Matus, J. E. Figueroa, R. A. Burgos, F. Nualart, K. D. Bhoola, C. D. Figueroa

Research output: Contribution to journalArticlepeer-review

65 Scopus citations

Abstract

Kinins are biologically active peptides that are powerful mediators of cellular inflammation. They mimic the cardinal signs of inflammation by inducing vasodilatation and by increasing vascular permeability and pain. Neutrophils are chemoattracted to sites of inflammation by several stimuli. However, the evidence concerning the chemotactic effect of kinin peptides has been contradictory. We analyzed the chemotactic effect of kinin B 1 receptor agonists on neutrophils isolated from peripheral blood of human healthy subjects. Chemotaxis was performed using the migration under agarose technique. To test the effect of B 1 receptor agonists, each assay was carried out overnight at 37°C in 5% CO 2-95% air on neutrophils primed with 1 ng/ml interleukin-1β. Simultaneous experiments were performed using unprimed cells or cells challenged with formyl-Met-Leu-Phe (fMLP). A clear chemotactic activity was observed when primed neutrophils were challenged with Lys-des[Arg 9]-bradykinin (LDBK) or des[Arg 9]-bradykinin at 10 -10 M but not when unprimed cells were used. A reduction in the chemotactic response was observed after priming of cells in the presence of 0.5 mM cycloheximide and 10 μg/ml brefeldin A, suggesting that some protein biosynthesis is required. Techniques such as reverse transcriptasepolymerase chain reaction and in situ hybridization confirmed the expression of the B 1 receptor mRNA, and immunocytochemistry and autoradiography demonstrated the expression of the B 1 receptor protein. In contrast to other chemoattractants such as fMLP, cytosolic intracellular calcium did not increase in response to the B 1 receptor agonist LDBK. A generation of kinin B 1 receptor agonists during the early phase of acute inflammation may favor the recruitment of neutrophils to the inflammatory site.

Original languageEnglish
Pages (from-to)117-124
Number of pages8
JournalJournal of Leukocyte Biology
Volume80
Issue number1
DOIs
StatePublished - Jul 2006
Externally publishedYes

Keywords

  • Bradykinin
  • Inflammation
  • Interleukin-1β
  • Kallikrein

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