AIRWAY RECRUITMENT OF LEUKOCYTES IN MICE IS DEPENDENT ON ALPHA(4)-INTEGRINS AND VASCULAR CELL-ADHESION MOLECULE-1

The involvement of the alpha(4)-integrin very late activation antigen 4 and vascular cell adhesion molecule-1 (VCAM-1) in leukocyte traffick ing into the airways of ovalbumin (OA)-sensitized and OA-challenged mi ce was investigated using in vivo administration of anti-alpha(4) mono clonal antibodies (mAb) PS/2, R1-2, and M/K-2.7 (MK2), specific for VC AM-1 VCAM-1 was upregulated on endothelial cells in lung tissue after OA inhalation. PS/2, R1-2, or MK2 significantly inhibited the recruitm ent of eosinophils and lymphocytes into the bronchoalveolar lavage (BA L) fluid and decreased inflammation in the lung tissues. Escalating in vivo doses of PS/2 or MK2 increased circulating levels of rat immunog lobulin G in the plasma. The binding of phycoery-therin-labeled anti-a lpha(4) mAb to blood T cells from PS/2-treated mice was reduced, imply ing that alpha(4) sites were already occupied. T cells and eosinophils in BAL fluid from mice treated with PS/2 or MK2 were phenotypically d ifferent from controls. Selective decreases of alpha(4)(+) T cells in the BAL fluid after PS/2 or MK2 treatment were coupled with changes in CD8(+), CD11a, and CD62L expression. The alpha(4)-integrin and VCAM-1 may have important roles in the antigen-induced recruitment of T cell s and eosinophils during OA-induced airway inflammation. The data sugg est that these adhesion molecules may be suitable targets for therapeu tic intervention in certain conditions of pulmonary inflammation.