TY - JOUR
T1 - CD48 Is critically involved in allergic eosinophilic airway inflammation
AU - Munitz, Ariel
AU - Bachelet, Ido
AU - Finkelman, Fred D.
AU - Rothenberg, Marc E.
AU - Levi-Schaffer, Francesca
PY - 2007/5/1
Y1 - 2007/5/1
N2 - 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.
AB - 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.
KW - 2B4
KW - Asthma
KW - CD2
KW - CD48
UR - http://www.scopus.com/inward/record.url?scp=34247614990&partnerID=8YFLogxK
U2 - 10.1164/rccm.200605-695OC
DO - 10.1164/rccm.200605-695OC
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C2 - 17290046
AN - SCOPUS:34247614990
SN - 1073-449X
VL - 175
SP - 911
EP - 918
JO - American Journal of Respiratory and Critical Care Medicine
JF - American Journal of Respiratory and Critical Care Medicine
IS - 9
ER -