The CC chemokine eotaxin/CCL11 has a selective profibrogenic effect on human lung fibroblasts

Ilaria Puxeddu, Reem Bader, Adrian Martin Piliponsky, Reuven Reich, Francesca Levi-Schaffer*, Neville Berkman

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

80 Scopus citations


Background: Eotaxin/CCL11 plays an important role in asthma. It acts through the chemokine receptor CCR3 expressed on hematopoietic and nonhematopoietic cells in the lung. Objective: To determine whether eotaxin/CCL11 modulates lung and bronchial fibroblast properties and thereby might contribute to airway remodeling. Methods: CCR3 expression was characterized on a lung fibroblast line (MRC-5; flow cytometry, fluorescent microscopy, RT-PCR, and Northern blotting), on primary bronchial fibroblasts (flow cytometry), and on fibroblasts in human lung tissue (confocal laser microscopy). The effects of eotaxin/CCL11 on lung fibroblast migration (Boyden chamber), proliferation (tritiated thymidine incorporation), α-smooth muscle actin expression (ELISA), 3-dimensional collagen gel contraction (floating gel), pro-α1(I) collagen mRNA (Northern blotting), total collagen synthesis (tritiated proline incorporation), matrix metalloproteinase activity (gelatin zymography), and TGF-β1 release (ELISA) were evaluated. The contribution of eotaxin/CCL11/CCR3 binding on lung fibroblasts was also investigated by neutralizing experiments. Results: CCR3 is constitutively expressed in cultured lung and primary bronchial fibroblasts and colocalizes with specific surface markers for human fibroblasts in lung tissue. Eotaxin/CCL11 selectively modulates fibroblast activities by increasing their proliferation, matrix metalloproteinase 2 activity, and collagen synthesis but not their differentiation into myofibroblasts, contractility in collagen gel, or TGF-β1 release. Eotaxin/CCL11 enhances migration of lung fibroblasts in response to nonspecific chemoattractants, and this effect is completely inhibited by anti-CCR3-neutralizing antibodies. Conclusion: These data demonstrate that eotaxin/CCL11 has a direct and selective profibrogenic effect on lung and bronchial fibroblasts, providing a novel mechanism whereby eotaxin/CCL11 can participate in airway remodeling in asthma.

Original languageAmerican English
Pages (from-to)103-110
Number of pages8
JournalJournal of Allergy and Clinical Immunology
Issue number1
StatePublished - Jan 2006

Bibliographical note

Funding Information:
Supported by a grant from the Aimwell Charitable Trust (FLS), the Israel Ministry of Health (NB), and the Israel Lung Association Tel Aviv (NB).


  • Airway remodeling
  • Asthma
  • CC chemokine
  • CCR3
  • Eotaxin/CCL11
  • Fibroblast
  • Myofibroblast
  • α-smooth muscle actin


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