Airway recruitment of leukocytes in mice is dependent on alpha4-integrins and vascular cell adhesion molecule-1

Author:

Chin J. E.1,Hatfield C. A.1,Winterrowd G. E.1,Brashler J. R.1,Vonderfecht S. L.1,Fidler S. F.1,Griffin R. L.1,Kolbasa K. P.1,Krzesicki R. F.1,Sly L. M.1,Staite N. D.1,Richards I. M.1

Affiliation:

1. Cell Biology and Inflammation Research and Drug DevelopmentToxicology, Pharmacia and Upjohn, Kalamazoo, Michigan 49001, USA.jia-en.chin@am.pnu.com

Abstract

The involvement of the alpha4-integrin very late activation antigen 4 and vascular cell adhesion molecule-1 (VCAM-1) in leukocyte trafficking into the airways of ovalbumin (OA)-sensitized and OA-challenged mice was investigated using in vivo administration of anti-alpha4 monoclonal antibodies (mAb) PS/2, R1-2, and M/K-2.7 (MK2), specific for VCAM-1. VCAM-1 was upregulated on endothelial cells in lung tissue after OA inhalation. PS/2, R1-2, or MK2 significantly inhibited the recruitment of eosinophils and lymphocytes into the bronchoalveolar lavage (BAL) fluid and decreased inflammation in the lung tissues. Escalating in vivo doses of PS/2 or MK2 increased circulating levels of rat immunoglobulin G in the plasma. The binding of phycoerytherin-labeled anti-alpha4 mAb to blood T cells from PS/2-treated mice was reduced, implying that alpha4 sites were already occupied. T cells and eosinophils in BAL fluid from mice treated with PS/2 or MK2 were phenotypically different from controls. Selective decreases of alpha4+ T cells in the BAL fluid after PS/2 or MK2 treatment were coupled with changes in CD8+, CD11a, and CD62L expression. The alpha4-integrin and VCAM-1 may have important roles in the antigen-induced recruitment of T cells and eosinophils during OA-induced airway inflammation. The data suggest that these adhesion molecules may be suitable targets for therapeutic intervention in certain conditions of pulmonary inflammation.

Publisher

American Physiological Society

Subject

Cell Biology,Physiology (medical),Pulmonary and Respiratory Medicine,Physiology

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