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CD48 Is Critically Involved in Allergic Eosinophilic Airway Inflammation

¹ Department of Pharmacology, School of Pharmacy, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel; ² Department of Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio; ³ Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio; and ⁴ David R. Bloom Center for Pharmacology, Hebrew University of Jerusalem, Jerusalem, Israel

Correspondence and requests for reprints should be addressed to Francesca Levi-Schaffer, Ph.D., Department of Pharmacology, School of Pharmacy, Faculty of Medicine, Hebrew University of Jerusalem, P.O. Box 12065, Jerusalem 91120, Israel. E-mail: fls{at}cc.huji.ac.il

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.

Key Words: asthma • CD48 • CD2 • 2B4

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject CD48 is an activation molecule able to facilitate various cellular activities. Its role in asthma is unknown. What This Study Adds to the Field CD48 is upregulated in experimental asthma. Anti-CD48–based therapies may be useful for asthma and perhaps various allergic diseases.

 

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