Dexamethasone inhibits prolonged survival and autocrine granulocyte-macrophage colony-stimulating factor production by human eosinophils cultured on laminin or tissue fibronectin

Garry Michael Walsh, A J Wardlaw

Research output: Contribution to journalArticlepeer-review

39 Citations (Scopus)


Background: Eosinophil autocrine generation of viability-promoting cytokines resulting from interaction with extracellular matrix (ECM) proteins may be important in promoting their persistence in allergic inflammation.

Objective: We examined eosinophil interaction with fibronectin, laminin, collagen, fibrinogen, hyaluronate, or vitronectin in terms of adhesion and for their ability to promote prolonged eosinophil survival by autocrine generation of IL-3, IL-5, or granulocyte-macrophage colony-stimulating factor (GM-CSF). The effect of dexamethasone was examined because it may inhibit integrin-dependent autocrine generation of viability-enhancing cytokines.

Methods: Microtiter wells were coated with different ECM proteins, and assays were performed to determine their levels of eosinophil adhesion, and tests were performed to determine their prolonged survival in culture, The receptors involved in these processes, the cytokines generated, and the effect of a dose range of dexamethasone were all examined.

Results: Eosinophils cultured for 3 days on laminin or tissue fibronectin exhibited dose-dependent prolonged survival, which was not seen with any other ECM protein. Unstimulated eosinophils adhered to wells coated with laminin or fibronectin but not to wells coated with any of the other ECM proteins that were tested, Laminin-dependent eosinophil adhesion and prolonged survival were inhibited by specific monoclonal antibodies to beta 1 and alpha 6 beta 1. Laminin-dependent survival was inhibited by a neutralizing antibody to GM-CSF, an anti-IL-5 antibody achieved a measurable hut insignificant inhibition of survival, and an antibody to IL-3 had no effect, Increasing concentrations of dexamethasone (maximal at 10(-7) mol/L) inhibited both laminin-and fibronectin-dependent enhanced eosinophil viability at 3 days, Eosinophils cultured on either laminin or fibronectin for 24 or 72 hours generated picogram quantities of GM-CSF, which were inhibited by the addition of dexamethasone (10(-7) mol/L).

Conclusion: We have confirmed that eosinophils adhere to laminin in an alpha 6 beta 1-dependent manner, and this interaction results in the autocrine generation of GM-CSF, which enhances eosinophil survival in culture. Both laminin and tissue fibronectin-dependent autocrine GM-CSF generation were inhibited by physiologically relevant concentrations of dexamethasone. This may represent an important mechanism by which glucocorticoids reduce the tissue eosinophilia in allergic disease.

Original languageEnglish
Pages (from-to)208-215
Number of pages8
JournalJournal of Allergy and Clinical Immunology
Issue number2
Publication statusPublished - Aug 1997


  • eosinophil
  • dexamethasone
  • laminin
  • fibronectin
  • extracellular matrix
  • cytokines
  • integrins
  • prolonged survival
  • VLA-4


Dive into the research topics of 'Dexamethasone inhibits prolonged survival and autocrine granulocyte-macrophage colony-stimulating factor production by human eosinophils cultured on laminin or tissue fibronectin'. Together they form a unique fingerprint.

Cite this