Therapeutic effects of anti-B7-1 antibody in an ovalbumin-induced mouse asthma model.
Allergic asthma is a chronic inflammatory disorder of airways, which is characterized by attacks provoked by exposure to so-called asthma triggers, such as pet dander, second-hand tobacco smoke, dust mites, and mold spores. B7-1 (CD80), perhaps one of the most studied co-stimulatory molecules involved in asthma, plays a key role in regulating allergen-induced T cell activation in asthma, probably through T cell recruitment and Th cell differentiation upon allergen provocation. The present study was designed to test the hypothesis that anti-B7-1 antibody has therapeutic effects in asthma by blocking B7-1/CD28 pathway. The asthma model was established by ovalbumin (OVA) sensitization and challenging in female Balb/c mice. One hour after the last induction, mice were sacrificed and whole lung lavage was conducted. Cell numbers in bronchoalveolar lavage fluid (BALF) were determined and the expression levels of IFN-gamma and IL-4 in supernatant were measured by an enzyme-linked immunosorbent assay method. Sedimental cells smears were stained with Wright's-Gimsa mixed coloring method. The B7-1 expression was detected by immunohistochemistry method with frozen tissue sections. The anti-B7-1 antibody treatment could alleviate asthmatic syndromes induced by OVA. The number of recoverable eosinophils in BALF in the anti-B7-1 antibody treated group was significantly lower than that in the control group (P<0.01) and the eosinophils peribronchial infiltration was remarkably reduced in anti-B7-1 treated asthmatic mice, based on histological evaluation. The treatment with the anti-B7-1 antibody induced IFN-gamma expression and decreased IL-4 expression, compared with the asthmatic control group (P<0.01). In conclusion, the anti-B7-1 antibody approach may provide a novel therapy for allergic asthma.
Ji
Wei
W
Department of Respiratory Diseases, Children's Hospital, Soochow University, Suzhou, People's Republic of China. szdxjiwei@gmail.com
Chen
Xuyan
X
Zhengrong
Chen
C
Yumin
Hu
H
Huang
Li
L
Qiu
Yuhua
Y
D000818:Animals; D018927:Anti-Asthmatic Agents; D000906:Antibodies / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D018122:B7-1 Antigen / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D004804:Eosinophils / Q000276:immunology / Q000473:pathology; D005260:Female; D007150:Immunohistochemistry; D007167:Immunotherapy; D007371:Interferon-gamma / Q000096:biosynthesis; D008168:Lung / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology*
D018927:Anti-Asthmatic Agents; D000906:Antibodies; D018122:B7-1 Antigen; D007371:Interferon-gamma; D010047:Ovalbumin