Changes in adhesion molecule expression during distinct patterns of immune cell migration in the inflamed lung.

Abstract

In response to antigen inhalation, immune cells including alveolar macrophages expressing a VIP1 receptor subtype (VIP1R), lymphocytes and leukocytes participate in the inflammatory event, migrating into and from vascular regions in lung tissue of sensitized mice. To analyze these migratory mechanisms of immune cells, we immunohistochemically examined the expression of the following: cellular adhesion molecules, lymphocyte function-associated antigen-1 (LFA-1) very late activation antigen-4 (VLA-4), and the alpha V (alpha v) subunit and their respective ligands, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and fibronectine; the examination was carried out in pulmonary tissue from days 0, 2, 6 and 12 following intratracheal administration of sheep red blood cells (SRBC) as an antigen to previously sensitized mice. Two days following the antigen challenge, VIP1R-positive macrophages strongly expressing the alpha v integrin subunit were found clustered on the endothelial surface and among the aggregates of perivascularly infiltrated leukocytes. On the endothelium of arteries, veins and capillaries, alpha v immunoreactivity was prominently reduced, whereas staining for fibronectin was enhanced more than the prechallenge control level. The blood vessel endothelium was also stained positive for VCAM-1 and ICAM-1, while many of the infiltrating lymphocytes were positive for VLA-4 and LFA-1 immunolabelings. By post-challenge, day 6, delta 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 perivascular region and located in the alveoli. VLA-4 bearing lymphocytes conspicuously increased in number among the perivascular leukocytes, while immunoreactivity for LFA-1, VCAM-1, ICAM-1 and fibronectin was unchanged from that for post-challenge day 2. The results indicate that the expression of the alpha v-bearing integrin and its ligand fibronectin drastically changes as pulmonary inflammatory responses. These changes in expression of adhesion molecules during immune response may play an important role in the dynamic regulation of VIP1R-positive macrophage migration in the lung parenchymal compartment.