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

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.

Tang ML ，Fiscus LC 《PULMONARY PHARMACOLOGY & THERAPEUTICS》

L-Selectin is required for the development of airway hyperresponsiveness but not airway inflammation in a murine model of asthma.

Fiscus LC ，Van Herpen J ，Steeber DA ，Tedder TF ，Tang ML ... -  《JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY》

L-selectin and intercellular adhesion molecule 1 mediate lymphocyte migration to the inflamed airway/lung during an allergic inflammatory response in an animal model of asthma.

Keramidaris E ，Merson TD ，Steeber DA ，Tedder TF ，Tang ML ... -  《JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY》

Leukocyte entry into sites of inflammation requires overlapping interactions between the L-selectin and ICAM-1 pathways.

Steeber DA ，Tang ML ，Green NE ，Zhang XQ ，Sloane JE ，Tedder TF ... -  《JOURNAL OF IMMUNOLOGY》

United airways: circulating Th2 effector cells in an allergic rhinitis model are responsible for promoting lower airways inflammation.

KleinJan A ，Willart M ，van Nimwegen M ，Leman K ，Hoogsteden HC ，Hendriks RW ，Lambrecht BN ... -  《-》