Submitted on May 12, 2005
Accepted on August 19, 2005
Antibody-Antigen Interaction in the Airway Drives Early Granulocyte Recruitment through BLT1
Benjamin D Medoff1, Andrew M Tager1, Ryan Jackobek2, Terry K Means2, Lan Wang3, and Andrew D Luster2*
1 Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Boston, MA, USA; Pulmonary and Critical Care Unit, Massachusetts General Hospital, Boston, MA, USA
2 Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Boston, MA, USA
3 Department of Pathology, Massachusetts General Hospital, Boston, MA, USA
* To whom correspondence should be addressed. E-mail: aluster{at}partners.org.
Antibody-antigen interactions in the airway initiate inflammation in acute asthma exacerbations. This inflammatory response is characterized by the recruitment of granulocytes into the airways. In murine models of asthma, granulocyte recruitment into the lung contributes to the development of airways hyper-responsiveness (AHR), mucus production and airway remodeling. Leukotriene B4 is a mediator released following antigen challenge that has chemotactic activity for granulocytes, mediated through its receptor, BLT1. We investigated the role of BLT1 in granulocyte recruitment following antigen challenge. Wild-type mice and BLT1-/- mice were sensitized and challenged with ovalbumin (OVA) to induce acute allergic airway inflammation. In addition, to explore the relevance to antibody-antigen interactions, we injected OVA bound to anti-OVA IgG1 or anti-OVA IgE intratracheally into naive wild-type and BLT1-/- mice. Cell composition of the lungs, cytokine levels, histology, and AHR were determined. Following sensitization and challenge with ovalbumin, there was significantly reduced neutrophil and eosinophil recruitment into the airways of BLT1-/- mice when compared to wild-type animals after 1 or 2 daily antigen challenges but this difference was not seen after 3 or 4 daily antigen challenges. Mucus production and AHR were not effected. Intratracheal injection of OVA bound to IgG1 or IgE induced neutrophil recruitment into the airways in wild-type mice but not in the BLT1-/- mice. We conclude that BLT1 mediates early recruitment of granulocytes into the airway in response to antigen-antibody interactions in a murine model of acute asthma.
