Airway recruitment of eosinophils and lymphocytes in mice is
dependent on [alpha]4 integrins and vascular cell adhesion molecule
-1.
Chin, Jia En, Cheryl A. Hatfield, Greg E. Winterrowd, John R.
Brashler, Steven L. Vonderfecht, Stephen F. Fidler, Robert L.
Griffin, Karen P. Kolbasa, Raymond F. Krzesicki, Laurel M. Sly, Nigel
D. Staite, and Ivan M. Richards.
Cell Biology and Inflammation Research and *Drug Development
Toxicology, Pharmacia and Upjohn, Inc., 301 Henrietta Street,
Kalamazoo, MI 49001
APStracts 3:0180L, 1996.
The involvement of the [alpha]4 integrin very late activation antigen
4 (VLA-4) and vascular cell adhesion molecule-1 (VCAM-1) in leukocyte
trafficking into the airways of ovalbumin (OA)-sensitized and
challenged mice was investigated using in vivo administration of
anti-[alpha]4 mAbs PS/2 and R1-2, and M/K-2.7 (MK2), specific for
VCAM-1. VCAM-1 was upregulated on endothelial cells in lung tissue
following 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 IgG in the plasma. The binding of
phycoerytherin (PE)-labeled anti-[alpha]4 mAb to blood T cells from
PS/2 treated mice was reduced, implying that [alpha]4 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 [alpha]4+ T cells in the BAL fluid after PS/2
or MK2 treatment were coupled with changes in CD8+, CD11a and CD62L
expression. [alpha]4 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.
Received 6 March 1996; accepted in final form 24 September 1996.
APS Manuscript Number L78-6.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 5 November 1996