Eosinophil trans-basement membrane migration induced by interleukin-8 and neutrophils

Am J Respir Cell Mol Biol. 2006 Jun;34(6):760-5. doi: 10.1165/rcmb.2005-0303OC. Epub 2006 Feb 2.


Neutrophilic inflammation observed with severe asthma is often associated with interleukin-8 (IL-8). Neutrophils can secrete a variety of mediators that may augment the migration of eosinophils. We have reported a positive correlation between the concentrations of neutrophils and eosinophils in sputum from subjects with severe asthma, suggesting a possible role of neutrophils in regulating eosinophilic inflammation. The aim of this study was to investigate whether neutrophils stimulated with IL-8 modify the trans-basement membrane migration (TBM) of eosinophils. Eosinophils and neutrophils were isolated from peripheral blood drawn from healthy donors or subjects with mild asthma. The TBM of eosinophils in response to IL-8 was evaluated in the presence or absence of neutrophils using the chambers with a Matrigel-coated transwell insert. Neither IL-8 alone nor the presence of neutrophils alone induced the TBM of eosinophils. However, when eosinophils were coincubated with neutrophils and stimulated with IL-8, the TBM of eosinophils was significantly augmented. This augmented TBM of eosinophils was inhibited by a matrix metalloproteinase-9 inhibitor, a leukotriene B4 receptor antagonist, platelet-activating factor antagonists, or an anti-TNF-alpha monoclonal antibodies. These results suggest that neutrophils migrated in response to IL-8 may lead eosinophils to accumulate in the airways of asthma and possibly aggravate this disease.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Antibodies, Monoclonal
  • Asthma / blood
  • Asthma / immunology
  • Azepines / pharmacology
  • Basement Membrane / immunology
  • Basement Membrane / metabolism
  • Chemotaxis, Leukocyte* / drug effects
  • Coculture Techniques
  • Collagen
  • Culture Media, Conditioned
  • Drug Combinations
  • Eosinophils / drug effects
  • Eosinophils / enzymology
  • Eosinophils / immunology*
  • Humans
  • Interleukin-8 / immunology*
  • Interleukin-8 / pharmacology*
  • Laminin
  • Leukotriene B4 / immunology
  • Leukotriene B4 / metabolism
  • Matrix Metalloproteinase 9 / immunology
  • Matrix Metalloproteinase 9 / metabolism
  • Neutrophil Activation
  • Neutrophils / drug effects*
  • Neutrophils / enzymology
  • Neutrophils / immunology*
  • Paracrine Communication
  • Platelet Activating Factor / immunology
  • Platelet Activating Factor / metabolism
  • Protease Inhibitors / pharmacology
  • Proteoglycans
  • Pulmonary Eosinophilia / immunology
  • Triazoles / pharmacology
  • Tumor Necrosis Factor-alpha / immunology
  • Tumor Necrosis Factor-alpha / metabolism


  • Antibodies, Monoclonal
  • Azepines
  • Culture Media, Conditioned
  • Drug Combinations
  • Interleukin-8
  • Laminin
  • Platelet Activating Factor
  • Protease Inhibitors
  • Proteoglycans
  • Triazoles
  • Tumor Necrosis Factor-alpha
  • WEB 2086
  • matrigel
  • Leukotriene B4
  • Collagen
  • Matrix Metalloproteinase 9