Therapeutic effects of anti-B7-H3 antibody in an ovalbumin-induced mouse asthma model.
BACKGROUND
B7 molecules play a key role in regulating allergen-induced T cell activation in asthma, which may occur through T cell recruitment and T helper cell differentiation on allergen provocation. Initial studies have shown that B7-H3 (CD276), a recently identified B7 family member, plays a critical role in the development of Th2 cells.


OBJECTIVE
To investigate the effects of anti-B7-H3 monoclonal antibody (mAb) in a mouse model of allergic asthma.


METHODS
The asthma model was established by ovalbumin (OVA) sensitization and challenging in female BALB/c mice. Total cell numbers in bronchoalveolar lavage fluid (BALF) were determined, and the expression levels of interferon gamma (IFN-γ), interleukin (IL)-4, and IL-17 in BALF were measured by enzyme-linked immunosorbent assay. Pulmonary eosinophil infiltration and mucus production were detected by hematoxylin and eosin (H&E) and periodic acid-Schiff (PAS), respectively. B7-H3 expression was detected by immunohistochemistry in frozen tissue sections.


RESULTS
Anti-B7-H3 mAb treatment alleviated the asthmatic syndrome, decreased the levels of B7-H3-positive cells in the lung tissues, abrogated hypercellularity, eosinophil infiltration, and mucus production, and inhibited IL-4 and IL-17 production in BALF at the induction phase as compared with the immunoglobulin G (IgG) control group (P < .01). In addition, the treatment of anti-B7-H3 mAb at the induction phase could increase the expression levels of IFN-γ as compared with the IgG control group (P < .01). Anti-B7-H3 mAb treatment at the effector phase did not inhibit the asthma response.


CONCLUSIONS
Blockade of B7-H3 signals may provide a novel therapeutic approach to the treatment of allergic asthma.
Department of Respiratory Disease, Children's Hospital Affiliated to Soochow University, Suzhou, China.
Zheng-Rong
ZR
Chen
Guang-Bo
GB
Zhang
Yu-Qing
YQ
Wang
Yong-Dong
YD
Yan
Wei-Fang
WF
Zhou
Canhong
C
Zhu
Ying
Y
Chen
Jian
J
Wang
Wei
W
Ji
D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology; D060887:B7 Antigens / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D016207:Cytokines / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D007074:Immunoglobulin G / Q000276:immunology; D007958:Leukocyte Count; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D018927:Anti-Asthmatic Agents; D000911:Antibodies, Monoclonal; D060887:B7 Antigens; C486038:Cd276 protein, mouse; D016207:Cytokines; D007074:Immunoglobulin G; D010047:Ovalbumin