CHANGES IN ADHESION MOLECULE EXPRESSION DURING DISTINCT PATTERNS OF IMMUNE CELL-MIGRATION IN THE INFLAMED LUNG

In response to antigen inhalation, immune cells including alveolar mac rophages expressing a VIP1 receptor subtype (VIP1R), lymphocytes and l eukocytes participate in the inflammatory event, migrating into and fr om vascular regions in lung tissue of sensitized mice. To analyze thes e migratory mechanisms of immune cells, we immunohistochemically exami ned the expression of the following: cellular adhesion molecules, lymp hocyte function-associated antigen-1 (LFA-1), very late activation ant igen-4 (VLA-4), and the alpha V (partial derivative v) subunit and the ir respective ligands, intercellular adhesion molecule-1 (ICAM-1), vas cular cell adhesion molecule-1 (VCAM-1), and fibronectine; the examina tion was carried out in pulmonary tissue from days 0, 2, 6 and 12 foll owing intratracheal administration of sheep red blood cells (SRBC) as an antigen to previously sensitized mice. Two days following the antig en challenge, VIP1R-positive macrophages strongly expressing the parti al derivative v integrin subunit were found clustered on the endotheli al surface and among the aggregates of perivascularly infiltrated leuk ocytes. On the endothelium of arteries, veins and capillaries, partial derivative v immunoreactivity was prominently reduced, whereas staini ng for fibronectin was enhanced more than the prechallenge control lev el. The blood vessel endothelium was also stained positive for VCAM-1 and ICAM-1, while many of the infiltrating lymphocytes were positive f or VLA-I and LFA-1 immunolabelings. By post-challenge, day 6, partial derivative v integrin subunit immunoreactivity was re-expressed on the blood vessel endothelium and only weakly expressed on VIP1R-positive macrophages, which were in retreat from the leukocyte-aggregating peri vascular region and located in the alveoli. VLA-4 bearing lymphocytes conspicuously increased in number among the perivascular leukocytes, w hile immunoreactivity for LFA-1, VCAM-1, ICAM-1 and fibronectin was un changed from that for post-challenge day 2. The results indicate that the expression of the partial derivative v-bearing integrin and its li gand fibronectin drastically changes as pulmonary inflammatory respons es. These changes in expression of adhesion molecules during immune re sponse may play an important role in the dynamic regulation of VIP1R-p ositive macrophage migration in the lung parenchymal compartment.