CD48 is critically involved in allergic eosinophilic airway inflammation.
BACKGROUND
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.


OBJECTIVE
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.


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.
Munitz
Ariel
A
Department of Pharmacology, School of Pharmacy, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.
Bachelet
Ido
I
Finkelman
Fred D
FD
Rothenberg
Marc E
ME
Levi-Schaffer
Francesca
F
D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D018801:CD2 Antigens / Q000235:genetics / Q000378:metabolism; D000071178:CD48 Antigen; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D011657:Pulmonary Eosinophilia / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism; D012130:Respiratory Hypersensitivity / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D000071176:Signaling Lymphocytic Activation Molecule Family
D015703:Antigens, CD; D018801:CD2 Antigens; D000071178:CD48 Antigen; C490007:Cd244a protein, mouse; C000604066:Cd48 protein, mouse; D016207:Cytokines; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D000071176:Signaling Lymphocytic Activation Molecule Family