Important roles for L-selectin and ICAM-1 in the development of allergic airway inflammation in asthma

M. L.K. Tang, L. C. Fiscus

Research output: Contribution to journalArticlepeer-review

55 Scopus citations

Abstract

Airway inflammation and airway hyperresponsiveness (AHR) are fundamental features of asthma. Migration of inflammatory cells from the circulation into the lungs is dependent upon adhesion molecule interactions. The cell surface adhesion molecules L-selectin and intercellular adhesion molecule (ICAM)-1 have been demonstrated to mediate leukocyte rolling on inflamed pulmonary endothelium, and ICAM-1 has also been shown to mediate capillary sequestration in inflamed lung. However, their roles in the development of airway inflammation and AHR in asthma have not been directly examined. We have characterised the roles of L-selectin and ICAM-1 in the recruitment of inflammatory cells to the lung and in the development of airway hyperresponsiveness using an ovalbumin (OVA)-induced allergic airway disease model of asthma and adhesion molecule-deficient mice. OVA-sensitized/challenged ICAM-1-deficient mice have dramatically reduced inflammatory influx into the airway/lung and a corresponding attenuation of AHR as compared to wild-type controls. OVA-sensitized/challenged L-selectin-deficient mice demonstrate significantly reduced numbers of CD3+lymphocytes and increased numbers of B220+ lymphocytes in BAL as compared to wild-type mice (P < 0.05). However, other parameters of airway/lung inflammation in OVA-sensitized/challenged L-selectin-deficient mice were equivalent to wild-type control mice. Remarkably, despite a fulminant inflammatory response in the airway/lung, AHR was completely abrogated in OVA-sensitized/challenged L-selectin-deficient mice. These findings suggest a crucial role for ICAM-1 in the development of airway inflammation and AHR in asthma. In contrast, L-selectin plays a more selective role in the development of airway hyperresponsiveness but not allergic inflammation in this animal model of asthma. Thus, L-selectin and ICAM-1 represent potential targets for novel asthma therapies specifically aimed at controlling airway inflammation and/or airway hyperresponsiveness.

Original languageEnglish (US)
Pages (from-to)203-210
Number of pages8
JournalPulmonary Pharmacology and Therapeutics
Volume14
Issue number3
DOIs
StatePublished - 2001

Keywords

  • Adhesion molecules
  • Asthma
  • Inflammation

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