CCR3 monoclonal antibody inhibits airway eosinophilic inflammation and mucus overproduction in a mouse model of asthma.
Acta Pharmacol Sin. 2006 Dec; 27(12):1594-9.AP

Abstract

AIM

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.

CONCLUSION

CCR3 mAb can significantly inhibit airway eosinophilia and mucus overproduction in asthmatic mice. Blockage of CCR3 may represent a new strategy to asthma therapy.

Links

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onlinelibrary.wiley.com
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Authors+Show Affiliations

Shen HH
Department of Respiratory Diseases, the Second Affiliated Hospital, Zhejiang University College of Medicine, Hangzhou 310009, China. hshen@mail.hz.zj.cn
Xu F
No affiliation info available
Zhang GS
No affiliation info available
Wang SB
No affiliation info available
Xu WH
No affiliation info available

MeSH

AnimalsAntibodies, MonoclonalAsthmaBronchoalveolar Lavage FluidEosinophiliaEosinophilsErbB ReceptorsGoblet CellsInterleukin-5Leukocyte CountLungMaleMiceMice, Inbred C57BLMucin 5ACMucinsMucusOvalbuminRNA, MessengerReceptors, CCR3Receptors, Chemokine

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17112414