AUTHOR=Johansson Mats W., Mosher Deane F.

TITLE=Integrin Activation States and Eosinophil Recruitment in Asthma

JOURNAL=Frontiers in Pharmacology

VOLUME=4

YEAR=2013

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2013.00033

DOI=10.3389/fphar.2013.00033

ISSN=1663-9812

ABSTRACT=<p>Eosinophil arrest and recruitment to the airway in asthma are mediated, at least in part, by integrins. Eosinophils express α<sub>4</sub>β<sub>1</sub>, α<sub>6</sub>β<sub>1</sub>, α<sub>L</sub>β<sub>2</sub>, α<sub>M</sub>β<sub>2</sub>, α<sub>X</sub>β<sub>2</sub>, α<sub>D</sub>β<sub>2</sub>, and α<sub>4</sub>β<sub>7</sub> integrins, which interact with counter-receptors on other cells or ligands in the extracellular matrix. Whether a given integrin-ligand pair mediates cell adhesion and migration depends on the activation state of the integrin. Integrins exist in an inactive bent, an intermediate-activity extended closed, and a high-activity extended open conformation. Integrin activation states can be monitored by conformation-specific monoclonal antibodies (mAbs). Studies in mice indicate that both β<sub>1</sub> and β<sub>2</sub> integrins mediate eosinophil recruitment to the lung. <italic>In vitro</italic> studies indicate that α<sub>4</sub>β<sub>1</sub> and α<sub>M</sub>β<sub>2</sub> are the principal integrins mediating eosinophil adhesion, including to vascular cell adhesion molecule-1 and the novel α<sub>M</sub>β<sub>2</sub> ligand periostin. <italic>In vivo</italic>, blood eosinophils have intermediate-activity β<sub>1</sub> integrins, as judged by mAb N29, apparently resulting from eosinophil binding of P-selectin on the surface of activated platelets, and have a proportion of their β<sub>2</sub> integrins in the intermediate conformation, as judged by mAb KIM-127, apparently due to exposure to low concentrations of interleukin-5 (IL-5). Airway eosinophils recovered by bronchoalveolar lavage (BAL) after segmental antigen challenge have high-activity β<sub>1</sub> integrins and high-activity α<sub>M</sub>β<sub>2</sub> that does not require IL-5. Here we review information on how the activation states of eosinophil β<sub>1</sub> and β<sub>2</sub> integrins correlate with measurements of eosinophil recruitment and pulmonary function in asthma. Blood eosinophil N29 reactivity is associated with decreased lung function under various circumstances in non-severe asthma and KIM-127 with BAL eosinophil numbers, indicating that intermediate-activity α<sub>4</sub>β<sub>1</sub> and α<sub>M</sub>β<sub>2</sub> of blood eosinophils are important for eosinophil arrest and consequently for recruitment and aspects of asthma.</p>