Timing of administration of anti-VLA-4 differentiates airway hyperresponsiveness in the central and peripheral airways in mice

Arihiko Kanehiro, Katsuyuki Takeda, Anthony Joetham, Adrian Tomkinson, Toshihide Ikemura, Charles G. Irvin, Erwin W. Gelfand

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

The development of airway hyperresponsiveness (AHR) is correlated with the infiltration into the lungs of activated eosinophils and T lymphocytes. In large part, influx of eosinophils into the lung is dependent on very late activating antigen-4 (VLA-4) expression. However, the kinetics of eosinophil recruitment and the development of AHR are not fully delineated. Airway function was monitored by changes in lung resistance (RL) and dynamic compliance (Cdyn) to methacholine (MCh) inhalation after anti-VLA-4. After ovalbumin (OVA) sensitization and airway challenge of BALB/c mice, AHR increased as did the number of lung inflammatory cells. Administration of anti-VLA-4 to sensitized mice 2 h before the first (of three) OVA airway challenges significantly prevented changes in RL. Moreover, injection of the antibody from 2 h before the first challenge to 42 h after the last challenge significantly prevented the increases in RL, as well as eosinophil and lymphocyte numbers in the bronchoalveolar lavage fluid (BALF); interleukin-5 (IL-5) and leukotriene concentrations in BALF were also significantly inhibited. Interestingly, treatment with anti-VLA-4 only prevented changes in Cdyn and goblet cell hyperplasia when administered 2 h before the first challenge. These studies demonstrate that the timing of anti-VLA-4 administration can selectively affect pathologic processes that contribute to altered airway function in the central and peripheral airways after allergen challenge.

Original languageEnglish
Pages (from-to)1132-1139
Number of pages8
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume162
Issue number3 I
DOIs
Publication statusPublished - Jan 1 2000

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

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