Cysteinyl leukotrienes induce human eosinophil locomotion and adhesion molecule expression via a CysLT1 receptor-mediated mechanism

L. Fregonese, M. Silvestri, F. Sabatini, G. A. Rossi

Research output: Contribution to journalArticlepeer-review

Abstract

Background: The mechanisms involved in eosinophil recruitment by cysteinyl-leukotrienes (CysLTs) remain to be defined. Objective: We investigated whether CysLTs LTC4, LTD4 and LTE4 could directly stimulate in vitro adhesion molecule expression and cell locomotion of blood eosinophils from atopic asthmatic donors. Methods: Mab staining and FACS analysis were used to evaluate Mac-1 and LFA-1 expression on eosinophils before and after CysLTs stimulation. Eosinophil locomotion was tested using a 48-well Boyden microchamber. Results: CysLTs, at the concentrations of 1 and 10 nM, were able to significantly up-regulate Mac-1 expression (P <0.05, each comparison) but not LFA-1 expression (P > 0.05, each comparison). A dose-dependant, eosinophil chemotaxis was also induced by LTC4, LTD4 and LTE4 (0.1 - 10 nM) (P <0.01, each comparison). Montelukast (0.01 nM to 10 nM), a specific CysLT1 receptor antagonist, significantly down-regulated LTC4, LTD4 and LTE4-indaced Mac-1 expression (P <0.01, each comparison) and the CysLT-indaced eosinophil migration (P <0.01, each comparison). In contrast, montelukast did not affect Mac-1 expression or cell migration when eosinophils were stimulated by the 'non-specific activators', such as fMLP or C5a (P > 0.05, each comparison). Conclusion: These data demonstrate that CysLTs are active in vitro in directly up-regulating human eosinophil functions involved in eosinophil recruitment. The down-regulation of Mac-1 expression and eosinophil chemotaxis by the potent and selective CysLT1 receptor antagonist montelukast indicated the specificity of the LTC4-, LTD4- and LTE4-induced response.

Original languageEnglish
Pages (from-to)745-750
Number of pages6
JournalClinical and Experimental Allergy
Volume32
Issue number5
DOIs
Publication statusPublished - 2002

Keywords

  • Adhesion molecules
  • Chemotaxis
  • Cysteinyl leukotrienes
  • Eosinophils
  • Mac-l
  • Montelukast

ASJC Scopus subject areas

  • Immunology

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