CD48 Is critically involved in allergic eosinophilic airway inflammation

Ariel Munitz, Ido Bachelet, Fred D. Finkelman, Marc E. Rothenberg, Francesca Levi-Schaffer*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

Rationale: Despite ongoing research, the molecular mechanisms controlling asthma are still elusive. CD48 is a glycosylphosphatidylinositol-anchored protein involved in lymphocyte adhesion, activation, and costimulation. Although CD48 is widely expressed on hematopoietic cells and commonly studied in the context of natural killer and cytotoxic T cell functions, its role in helper T cell type 2 settings has not been examined. Objectives: To evaluate the expression and function of CD48, CD2, and 2B4 in a murine model of allergic eosinophilic airway inflammation. Methods: Allergic eosinophilic airway inflammation was induced by ovalbumin (OVA)-alum sensitization and intranasal inoculation of OVA or, alternatively, by repeated intranasal inoculation of Aspergillus fumigatus antigen in wild-type, STAT (signal transducer and activator of transcription)-6-deficient, and IL-4/IL-13-deficient BALB/c mice. Gene profiling of whole lungs was performed, followed by Northern blot and flow cytometric analysis. Anti-CD48, -CD2, and -2B4 antibodies were administered before OVA challenge and cytokine expression and histology were assessed. Measurements and Main Results: Microarray data analysis demonstrated upregulation of CD48 in the lungs of OVA-challenged mice. Allergen-induced CD48 expression was independent of STAT-6, IL-13, and IL-4. Neutralization of CD48 in allergen-challenged mice abrogated bronchoalveolar lavage fluid and lung inflammation. Neutralization of CD2 inhibited the inflammatory response to a lesser extent and neutralization of 2B4 had no effect. Conclusions: Our results suggest that CD48 is critically involved in allergic eosinophilic airway inflammation. As such, CD48 may provide a new potential target for the suppression of asthma.

Original languageAmerican English
Pages (from-to)911-918
Number of pages8
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume175
Issue number9
DOIs
StatePublished - 1 May 2007

Keywords

  • 2B4
  • Asthma
  • CD2
  • CD48

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