Chemotaxis of alveolar macrophages in response to signals derived from alveolar epithelial cells.
We have postulated that alveolar epithelial cells (AEC) play a critical role in local regulation of alveolar macrophage (AM) recruitment and activation for host defense in the lung. The present study explores the 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 that rat AEC express the chemokines RANTES (regulated on activation, normal T expressed and secreted) and monocyte chemoattractant protein 1 (MCP-1) as well as granulocyte-macrophage colony-stimulating factor (GM-CSF). Neutralizing antibodies to RANTES and to MCP-1 and immunoprecipitation of GM-CSF decreased the chemotactic activity of AEC-CM by 58%, 29%, and 47%, respectively. Similar levels of chemotaxis were found in response to recombinant RANTES, MCP-1, and GM-CSF. In each instance the optimal dose was very low (0.01 to 0.1 ng/ml), with diminished chemotaxis at higher doses. Peritoneal macrophages (PM) also migrated in response to AEC-CM and each of the recombinant cytokines; however, AM were much more sensitive to AEC-CM, RANTES, and GM-CSF than were PM. AM migrated preferentially from medium conditioned by unstimulated AEC toward supernatants from interleukin 1alpha-stimulated AEC. Therefore, AEC may control the distribution of AM through the creation of local chemotactic gradients and are likely to play a critical role in the host response to low-level antigen entry into the peripheral lung.
O'Brien
A D
AD
Department of Internal Medicine, University of Michigan, and the Veterans Affairs Medical Center, Ann Arbor, USA.
Standiford
T J
TJ
Christensen
P J
PJ
Wilcoxen
S E
SE
Paine
R
R
D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D002465:Cell Movement / Q000502:physiology; D018932:Chemokine CCL2 / Q000276:immunology / Q000494:pharmacology; D018946:Chemokine CCL5 / Q000276:immunology / Q000494:pharmacology; D002630:Chemotactic Factors / Q000494:pharmacology; D002633:Chemotaxis / Q000187:drug effects / Q000502:physiology*; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004847:Epithelial Cells / Q000502:physiology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology / Q000502:physiology; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000502:physiology*; D017737:Macrophages, Peritoneal / Q000187:drug effects; D008297:Male; D011650:Pulmonary Alveoli / Q000166:cytology / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology
D000906:Antibodies; D018932:Chemokine CCL2; D018946:Chemokine CCL5; D002630:Chemotactic Factors; D017077:Culture Media, Conditioned; D016178:Granulocyte-Macrophage Colony-Stimulating Factor