Primary human alveolar type II epithelial cell CCL20 (macrophage inflammatory protein-3alpha)-induced dendritic cell migration.
Inhalation of antigenic matter stimulates rapid recruitment of dendritic cells (DCs) into the lung. Recent studies propose that the chemokine CCL20 (macrophage inflammatory protein-3alpha) may play an important role in DC recruitment. We previously showed that primary human alveolar type II epithelial (ATII) cells are a rich source of chemokines and so hypothesized that the ATII cell produces CCL20 and might therefore be a key regulator of DC recruitment into the lung. Here, we show that primary human ATII cells, but not human alveolar macrophages, produce CCL20 both constitutively (403.5 +/- 85.4 pg/ml; 24 h) and in response to endotoxin (lipopolysaccharide) exposure (1,525.0 +/- 169.4 pg/ml; 1 mug/ml lipopolysaccharide; 24 h) in a time- and dose-dependent manner. In addition, we show that peripheral blood monocyte-derived CD1a+ DCs migrate in response to conditioned media from ATII cells but not those from alveolar macrophages; DC migration was significantly correlated with the amount of CCL20 (r(2) > 0.9; P < 0.05) detected in the media but not with any other chemokine measured. We therefore conclude that the alveolar epithelium is an important source of CCL20 in the lung and that the ATII cell may play a critical role in controlling the movement of DCs through the lung both under normal and inflammatory conditions.
Thorley
Andrew J
AJ
Lung Cell Biology, National Heart & Lung Institute, Imperial College, Dovehouse Street, London SW3 6LY, UK.
Goldstraw
Peter
P
Young
Alan
A
Tetley
Teresa D
TD
D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D054418:Chemokine CCL20; D019742:Chemokines, CC / Q000096:biosynthesis*; D017077:Culture Media, Conditioned; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008070:Lipopolysaccharides / Q000494:pharmacology; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis*; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000276:immunology; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects / Q000276:immunology*
C108355:CCL20 protein, human; D054418:Chemokine CCL20; D019742:Chemokines, CC; D017077:Culture Media, Conditioned; D008070:Lipopolysaccharides; D019402:Macrophage Inflammatory Proteins