CHEMOTAXIS OF ALVEOLAR MACROPHAGES IN RESPONSE TO SIGNALS DERIVED FROM ALVEOLAR EPITHELIAL-CELLS

We have postulated that alveolar epithelial cells (AEC) play a critica l role in local regulation of alveolar macrophage (AM) recruitment and activation for host defense in the lung. The present study explores t he effects of conditioned medium from AEC (AEC-CM) on the migration of AM, using a Boyden chamber assay. AEC-CM was chemotactic for AM, with peak activity observed with a 1:10 dilution. We previously showed tha t rat AEC express the chemokines RANTES (regulated on activation, norm al T expressed and secreted) and monocyte chemoattractant protein 1 (M CP-I) as well as granulocyte-macrophage colony-stimulating factor (GMC SF), Neutralizing antibodies to RANTES and to MCP-I and immunoprecipit ation of GM-CSF decreased the chemotactic activity of AEC-CM by 58%, 2 9%, and 47%, respectively. Similar levels of chemotaxis were found in response to recombinant RANTES, MCP-I, and GM-CSF, In each instance th e optimal dose was very low (0.01 to 0.1 ng/ml), with diminished chemo taxis at higher doses. Peritoneal macrophages (PM) also migrated in re sponse to AEC-CM and each of the recombinant cytokines; however, AM we re much more sensitive to AEC-CM, RANTES, and GM-CSF than were PM. AM migrated preferentially from medium conditioned by unstimulated AEC to ward supernatants from interleukin 1 alpha-stimulated AEC. Therefore, AEC may control the distribution of AM through the creation of local c hemotactic gradients and are likely to play a critical role in the hos t response to low-level antigen entry into the peripheral lung.