Maturation of DC is associated with changes in motile characteristics and adherence.
Migration of dendritic cells (DC) from sentinel sites to lymphoid tissue entails the initiation and coordination of a complex series of cytoskeletal rearrangements resulting in polarised protrusion, formation of new adhesion points, and detachment. Although many diverse receptor-ligand interactions stimulating DC maturation and migration have been identified, the changes that occur in the structure of the actin cytoskeleton during these processes have received little attention. When derived in vitro, immature DC floated in clumps, and upon addition of maturation stimuli such as lipopolysaccharide (LPS), they rapidly adhered, developed polarity, and assembled actin-rich structures known as podosomes at the leading edge of the cell. Podosome assembly was associated with the specific recruitment of beta2 integrins, which in the absence of the Wiskott Aldrich Syndrome protein (WASp), did not occur. As maturation progressed, normal DC once again became rounded and devoid of podosomes. This change in morphology was closely associated with a quantitatively reduced ability to adhere to fibronectin or ICAM-1-coated surfaces. In immature DC, failure to form podosomes or selective inhibition of the CD18 component of podosomes resulted in a similarly reduced ability to adhere to ICAM-1, indicating that podosomes, through CD18, are necessary for tight adhesion to this ligand. We, therefore, propose that podosomes provide an essential link between directional cell protrusion and achievement of DC translocation by establishing new dynamic anchor points at the front of the cell. The temporal regulation of podosome assembly during DC maturation also suggests that they may be most critical for early movement, perhaps during transmigration of lymphatic endothelium.
Burns
Siobhan
S
Molecular Immunology Unit, Institute of Child Health, University College London, 30 Guilford Street, London, United Kingdom. s.burns@ich.ucl.ac.uk
Hardy
Samantha J
SJ
Buddle
Joanna
J
Yong
Kwee L
KL
Jones
Gareth E
GE
Thrasher
Adrian J
AJ
D018845:CD11 Antigens / Q000378:metabolism; D018821:CD18 Antigens / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology*; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D011506:Proteins / Q000378:metabolism; D051316:Wiskott-Aldrich Syndrome Protein
D018845:CD11 Antigens; D018821:CD18 Antigens; D008070:Lipopolysaccharides; D011506:Proteins; C495767:WAS protein, human; D051316:Wiskott-Aldrich Syndrome Protein; D018799:Intercellular Adhesion Molecule-1