CCR3 monoclonal antibody inhibits airway eosinophilic inflammation and mucus overproduction in a mouse model of asthma.
OBJECTIVE
To explore the effect of a rat anti-mouse CC-chemokine receptor-3 (CCR3) monoclonal antibody (CCR3 mAb) on airway eosinophilia and mucus overproduction in asthmatic mice.


METHODS
An asthma model was sensitized and challenged by ovalbumin (OVA) in male C57BL/6 mice. Asthmatic mice were given dual administration (intraperitoneal injection and aerosol inhalation) of CCR3 mAb or nonspecific rat IgG (ns-IgG). The number of total and differential inflammatory cells in the bronchial alveolar lavage fluid (BALF) was counted. Eosinophils number, the goblet cell percentage (GCP) and airway mucus index (AMI) were measured in the lung tissues. Interleukin (IL)-5 levels in the BALF were examined. The expression of MUC5AC and the epidermal growth factor receptor (EGFR) mRNA in the lung tissues was detected by semi-quantitative RT-PCR. The results were compared among the groups.


RESULTS
CCR3 mAb significantly suppressed the increased eosinophils in the BALF and lung tissues in OVA-challenged mice compared with ns-IgG-treated mice. IL-5 levels in the BALF in CCR3 mAb and ns-IgG administration mice exhibited no obvious changes relative to OVA-challenged asthmatic mice. CCR3 mAb reduced the increased GCP and AMI after OVA challenge and decreased the enhanced expression of MUC5AC and EGFR mRNA in lung tissues in asthmatic animals.


CONCLUSIONS
CCR3 mAb can significantly inhibit airway eosinophilia and mucus overproduction in asthmatic mice. Blockage of CCR3 may represent a new strategy to asthma therapy.
Shen
Hua-hao
HH
Department of Respiratory Diseases, the Second Affiliated Hospital, Zhejiang University College of Medicine, Hangzhou 310009, China. hshen@mail.hz.zj.cn
Xu
Feng
F
Zhang
Gen-sheng
GS
Wang
Shao-bin
SB
Xu
Wei-hua
WH
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001249:Asthma / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D004802:Eosinophilia / Q000473:pathology; D004804:Eosinophils / Q000473:pathology; D066246:ErbB Receptors / Q000096:biosynthesis / Q000235:genetics; D020397:Goblet Cells / Q000473:pathology; D015848:Interleukin-5 / Q000378:metabolism; D007958:Leukocyte Count; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D055271:Mucin 5AC; D009077:Mucins / Q000096:biosynthesis* / Q000235:genetics; D009093:Mucus / Q000378:metabolism*; D010047:Ovalbumin; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D054397:Receptors, CCR3; D019707:Receptors, Chemokine / Q000276:immunology*
D000911:Antibodies, Monoclonal; C515351:Ccr3 protein, mouse; C515352:Ccr3 protein, rat; D015848:Interleukin-5; C524679:Muc5ac protein, mouse; C524680:Muc5ac protein, rat; D055271:Mucin 5AC; D009077:Mucins; D012333:RNA, Messenger; D054397:Receptors, CCR3; D019707:Receptors, Chemokine; D010047:Ovalbumin; D066246:ErbB Receptors