Complete Dependence on CD4+ Cells in Late Asthmatic Response, but Limited Contribution of the Cells to Airway Remodeling in Sensitized Mice

• Nabe Takeshi

  Department of Pharmacology, Kyoto Pharmaceutical University, Japan

• Morishita Toyoko

  Department of Pharmacology, Kyoto Pharmaceutical University, Japan

• Matsuya Kouki

  Department of Pharmacology, Kyoto Pharmaceutical University, Japan

• Ikedo Ayumu

  Department of Pharmacology, Kyoto Pharmaceutical University, Japan

• Fujii Masanori

  Department of Pharmacology, Kyoto Pharmaceutical University, Japan

• Mizutani Nobuaki

  Department of Pharmacology, Kobe Pharmaceutical University, Japan

• Yoshino Shin

  Department of Pharmacology, Kobe Pharmaceutical University, Japan

Abstract

It is known that the late asthmatic response (LAR), a characteristic feature of asthma, is closely associated with CD4⁺ Th2 cell–mediated allergic inflammation. Airway remodeling is also a pathogenesis of asthma, but literature reporting roles of CD4⁺ cells in the remodeling is controversial. There has been no study that simultaneously assessed the roles of CD4⁺ cells in both LAR and airway remodeling. Sensitized mice were intratracheally challenged with ovalbumin 4 times. Treatment with an anti-CD4 monoclonal antibody (mAb) before the 1st challenge almost completely abolished increase in CD4⁺ cells in the tissues after the 4th challenge. The late phase increase in airway resistance after the 4th challenge was also completely inhibited by anti-CD4 mAb. Parameters of airway remodeling, subepithelial fibrosis and epithelial thickening were attenuated by treatment, whereas the inhibition was only 30% – 40%. Bronchial smooth muscle thickening was not affected. Because interleukin (IL)-5 production as well as eosinophilia was effectively suppressed by anti-CD4 mAb, the effect of anti-IL-5 mAb was also examined, resulting in no inhibition of airway remodeling. Collectively, although the LAR was completely dependent on CD4⁺ cell activation, airway remodeling was only partially dependent on the cell.

Journal

• Journal of Pharmacological Sciences

  Journal of Pharmacological Sciences 116 (4), 373-383, 2011

  The Japanese Pharmacological Society

Keywords

• airway remodeling
• late asthmatic response
• CD4<SUP>+</SUP> cell
• interleukin-5
• fibrosis

Details

• CRID: 1390282680155077248
• NII Article ID: 10029895650
• NII Book ID: AA11806667
• DOI: 10.1254/jphs.11083fp
• COI: 1:CAS:528:DC%2BC3MXhtFaqtrrN
• ISSN: 13478648
• ISSN: 13478613
• NDL BIB ID: 11206974
• PubMed: 21778663
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I11206974
• Web Site: https://search.jamas.or.jp/link/ui/2012183517
• Text Lang: en
• Data Source:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
  • KAKEN
• Abstract License Flag: Disallowed