Modulation of dendritic cell trafficking to and from the airways.
We investigated the fate of latex (LX) particles that were introduced into mice intranasally. Macrophages acquired the vast majority of particles and outnumbered LX particle-bearing airway dendritic cells (DCs) by at least two orders of magnitude. Yet alveolar macrophages were refractory to migration to the draining lymph node (DLN), and all transport to the DLN could be ascribed to the few LX(+) airway DCs. Upon macrophage depletion, markedly greater numbers of DCs were recruited into the alveolar space. Consequently, the number of DCs that carried particles to the DLN was boosted by 20-fold. Thus, a so far overlooked aspect of macrophage-mediated suppression of airway DC function stems from the modulation of DC recruitment into the airway. This increase in DC recruitment permitted the development of a robust assay to quantify the subsequent migration of DCs to the DLN. Therefore, we determined whether lung DCs use the same molecules that skin DCs use during migration to DLNs. Like skin DCs, lung DCs used CCR7 ligands and CCR8 for emigration to DLN, but the leukotriene C(4) transporter multidrug resistance-related protein 1 did not mediate lung DC migration as it does in skin, indicating that pathways governing DC migration from different tissues partially differ in molecular regulation.
Jakubzick
Claudia
C
Department of Gene and Cell Medicine, Mount Sinai School of Medicine, 1425 Madison Avenue, New York, NY 10029, USA.
Tacke
Frank
F
Llodra
Jaime
J
van Rooijen
Nico
N
Randolph
Gwendalyn J
GJ
D000818:Animals; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology; D007840:Latex / Q000276:immunology; D008198:Lymph Nodes / Q000166:cytology; D008264:Macrophages / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010586:Phagocytes / Q000166:cytology / Q000276:immunology; D010641:Phenotype; D012137:Respiratory System / Q000098:blood supply / Q000166:cytology* / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology
D007840:Latex